To assess the food effects and pharmacokinetic profile of oral prednisone (test preparation,5 mg) and prednisolone tablets (reference preparation,5 mg) using a randomized, two-period, two crossover, single-dose, fast and fed trial in 48 (24 in fast, 24 in fed) healthy Chinese adult subjects. In the trial, the plasma concentrations were determined at different time points up to 24 h and the pharmacokinetic parameters were analyzed according to the concentration data by non-compartmental analysis using WinNonlin software. All laboratory parameters, vital signs and adverse events (AEs) were monitored and recorded under the supervision of the clinicians throughout the whole process of the study. Prednisone and prednisolone undergo interconversion in liver. On average, the bioavailability of prednisolone after oral prednisone is approximately 80 http://www.chinadrugtrials.org.cn/ at 11 March 2020. • The food effects and pharmacokinetic evaluation of prednisone acetate and prednisolone were investigated in healthy Chinese subjects. • Prednisone and prednisolone undergo interconversion in liver. On average, the bioavailability of prednisolone after oral prednisone is approximately 80

As a common dermatosis, atopic dermatitis (AD) is primarily driven by type 2 inflammation. Sappanone A (SA), derived from the traditional medicinal plant Caesalpinia sappan L., has demonstrated a broad range of anti-inflammatory activities in various diseases. However, the pharmacological mechanisms underlying its efficacy remain unelucidated in AD. The objective of our research was to investigate the therapeutic efficacy and molecular mechanisms of SA in treating AD. In vitro, the anti-inflammatory effects of SA were evaluated in IL-4/IL-13/TNF-α stimulated HaCaT cells. In vivo, mice were treated with SA following the induction of AD-like symptoms with MC903 and assessed for inflammatory parameters. Furthermore, transcriptomics and network pharmacology were utilized to elucidate the therapeutic mechanisms of SA in AD. SA significantly suppressed the generation of type 2 inflammatory cytokines in HaCaT cells stimulated by IL-4/IL-13/TNF-α and alleviated MC903-induced AD-like symptoms in C57BL/6J mice. The integration of transcriptomics and network pharmacology displayed that SA regulated the type 2 inflammatory response in AD through the IL-21R-mediated JAK1/STAT3 signaling pathway. SA exerted a strong anti-inflammatory role in treating AD by inhibiting the activation of the JAK1/STAT3 signaling pathway mediated by IL-21R. This research not only supports the potential of SA as a novel agent for treating AD, but also offers methods for studying compounds derived from natural herbs in AD therapy.

The clinical effectiveness of vemurafenib that targets BRAF V600E mutation in patients with melanoma had been recognized. However, the drug resistance severely hampers the clinical application of vemurafenib. We combined metabolomics and transcriptomics analysis and found that phospholipase D2 (PLD2), a key enzyme in choline metabolism, was significantly highly expressed in vemurafenib-resistant melanoma cells, and knockdown of PLD2 significantly increased the drug sensitivity of vemurafenib in melanoma resistant cells. Furtherly, we found that the transcription factor forkhead box protein A1 (FOXA1) positively regulated the expression of PLD2 and promoted the resistance of vemurafenib. Importantly, the knockdown of PLD2 significantly enhanced the DNA breaks induced by vemurafenib treatment, which prompted that PLD2-mediated protection from vemurafenib was responsible for the drug resistance of vemurafenib. In addition, we furtherly found that the combination of PLD2 inhibitor CAY10594 or PLD1/PLD2 dual inhibitors FIPI and vemurafenib exerted synergistic antiproliferative effects in melanoma sensitive cells. The implementation of our study systematically clarified the molecular mechanism by which the FOXA1/PLD2 functional axis mediated vemurafenib resistance via protection from DNA breaks likely subsequent to apoptosis induction in melanoma, and proposed that targeted inhibition of PLD2 synergistically enhances the efficacy of vemurafenib or reverses its resistance, which provided us new insight for the clinical precision medicine of vemurafenib in melanoma.

Psoriasis is a prevalent immune-mediated inflammatory skin disease characterized by excessive abnormal proliferation of keratinocytes and infiltration of immune cells, which have significant impact on the life quality of individuals. Although biological agents and small molecule targeted drugs have brought significant clinical benefits to psoriasis patients, adverse reactions and high prices remains key issues in clinical medication of psoriasis, while natural product monomers possess high efficiency, low toxicity, anti-inflammatory and immunomodulatory properties, and bring new hope for the clinical treatment of psoriasis. Sappanone A (SA), a small molecule compound isolated from Caesalpinia sappan L, exhibits significant anti-inflammatory properties in various models, such as kidney inflammation and LPS-induced mice inflammation. Among these effects, the anti-inflammatory property of SA has received significant attention. In our study, we found that SA exhibited anti-proliferation and anti-inflammatory effects in HaCaT cells, and significantly alleviated imiquimod-induced psoriasis-like skin lesions via the inhibition of the excessive proliferation of keratinocytes and the infiltration of lymphocytes. Furthermore, the combinational analysis of network pharmacology and transcriptome sequencing revealed that SA exerted anti-psoriasis effects by inhibiting the matrix metalloproteinase 8 (Mmp8) expression and IL-17 pathway activation. In summary, we have first demonstrated that SA can be used as a novel anti-psoriasis drug, which may provide a novel strategy for the clinical treatment of psoriasis.

Background: Ursolic acid is a triterpenoid compound found in natural plants that exhibits antiproliferative effects in various cancer cells. Our study is the first to demonstrate the strong inhibitory effects of ursolic acid on the proliferation of cutaneous T-cell lymphoma (CTCL) cells. We aimed to further investigate the underlying mechanism of the proliferation inhibition induced by ursolic acid in CTCL cells using transcriptome sequencing. Methods: Cell counting kit-8 assays were used to observe the effects of six traditional medicine monomers on the proliferation of CTCL cells. Transcriptome sequencing was used to identify differentially expressed genes after ursolic acid treatment. Bioinformatics analysis was performed to determine the potential mechanism. Real-time quantitative PCR and western blotting analyses were performed to confirm the sequencing results and verify the possible mechanisms of ursolic acid-mediated proliferation inhibition in CTCL cells. Results: Ursolic acid exhibited the strongest inhibitory effect on the proliferation of CTCL cells among the six traditional medicine monomers. Transcriptome sequencing analysis showed that 2,466 genes were significantly altered. Combined with Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis and protein-protein interaction network analysis, the interaction of various pathways and signaling molecules, such as tumor necrosis factor-alpha, NLR family pyrin domain containing 1, c-Jun N-terminal kinase, and melanoma differentiation-associated gene 5, accounted for the anti-tumor effects of ursolic acid in CTCL cells. Conclusion: Ursolic acid significantly inhibited the proliferation of CTCL cells, and our study laid a theoretical foundation for the future treatment of CTCL using ursolic acid.

Background EMLA cream is a local anesthetic. The pharmacokinetics and dermal effects of a topical anesthetic formulation has not been evaluated in healthy Chinese volunteers. Materials and methods The Pharmacokinetics of the lidocaine/prilocaine test (T) or reference (R, EMLA) cream were evaluated in a fasting, single-dose, two-period crossover bioequivalent study conducted in 40 healthy Chinese volunteers. Meanwhile, the dermal effects including blanching, erythema, temperature sensation, edema, and skin rash were also evaluated during the study. Results After applied 15 g of the cream for 4 h to a 100 cm 2 area under plastic occlusive film on the skin of the thigh of healthy volunteers, the results of the pharmacokinetic study showed that the active components absorbed in skin from topical products was relatively low compared with most system absorption drugs. After the removal of the residual anesthetic cream, there was a vascular biphasic response with initial transient blanching which reaches a peak at 4.5 h and later more persisting period erythema. The change of temperature sensory sensitivity reached the peak value at 4.5-6 h.There was no statistically significant difference of the changes after application the lidocaine/prilocaine T or R cream in subjects. In general, the lidocaine/prilocaine T or R cream was well tolerated. Conclusion The method described a model for investigations of pharmacokinetics and pharmacodynamics of topical lidocaine/prilocaine cream. Except the plasma drug level indicator, these pharmacodynamics data should also be evaluated in the anesthetic transdermal pharmacokinetics study. Clinical Trial Registration CTR20211544; registered in http://www.chinadrugtrials.org.cn/ at September 2021.

新型冠状病毒肺炎的发生,给我国各行业都造成了巨大的影响,对临床试验的顺利开展也带来了很多的困难.目前来看,长期抗疫已经不可避免,疫情期间开展临床试验已经成为常态.临床试验中,应该将保护受试者的安全放在首位.本文介绍中国医学科学院皮肤病医院Ⅰ期临床在2020年5月至2020年12月开展的5个临床试验项目,通过试验前期、筛选期、试验期、清洗期、随访期采取的一系列措施,保障受试者的安全,确保临床试验顺利地进行,从而确保试验数据和结果的可靠性、完整性.

Glass ampoules are currently commonly used for clinical small-volume injections, and they are difficult to keep in original packaging in clinical medication management and actual application. The drug mark on the surface of the glass ampoule is easily erased after being repeatedly rubbed, which makes the handwriting blurred and unrecognizable. Moreover, there is the possibility of accidental slipping and breaking during use.

目的 研究非那雄胺在中国健康志愿者使用中的安全性,为临床合理用药提供参考.方法 通过2项单次口服5 mg非那雄胺受试制剂和参比制剂的随机、双交叉、2周期的生物等效性研究,共103名中国健康男性志愿者完成了空腹和高脂餐后试验,监测并记录实验室检查参数、生命体征和不良事件.结果 2项试验中,非那雄胺均耐受良好,没有发生严重不良反应.实验室检查异常的不良事件中,血清胆红素水平升高出现的频次最多,最长在10 d内恢复至正常.结论 非那雄胺是一种有效的、选择性的UGT1A4竞争性抑制剂,在血清胆红素的代谢中起关键作用.非那雄胺可能导致血清胆红素升高,建议临床用药时应注意与非那雄胺相关的血清胆红素升高风险.

Objective:To evaluate the inhibitory effect of a retinoid derivative ECPIRM on proliferation of a cutaneous T-cell lymphoma (CTCL) cell line HH, and to explore its potential mechanisms.Methods:Cultured HH cells were treated with ECPIRM at different concentrations of 0 (control group) , 5, 10 and 20 μmol/L separately for 72 hours, cell counting kit-8 (CCK8) assay was performed to evaluate the effect of ECPIRM on the proliferative activity of HH cells, and flow cytometry to investigate the effect of ECPIRM on apoptosis of HH cells. Some HH cells were treated with 10 μmol/L ECPIRM for 72 hours, transcriptome sequencing was performed to investigate gene expression changes triggered by ECPIRM in HH cells, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and gene ontology (GO) enrichment analysis were then performed to analyze differentially expressed genes in HH cells induced by ECPIRM. Reverse transcription-qPCR was subsequently conducted to verify changes in key gene expression in related pathways. Intergroup differences were analyzed by using one-way analysis of variance, and least significant difference (LSD) - t test was used for multiple comparisons. Results:CCK8 assay showed that the 50% inhibitory concentration (IC50) of ECPIRM on HH cells was 4.91 ± 2.48 μmol/L, the viability of HH cells significantly differed among the control group, and 5-, 10-and 20-μmol/L ECPIRM groups (100.00% ± 2.87%, 49.58% ± 4.53%, 48.36% ± 2.88%, 31.44% ± 2.46%, respectively, F=162.86, P < 0.001) , and was significantly lower in the 5-, 10-and 20-μmol/L ECPIRM groups than in the control group ( t=15.36, 15.73, 20.89, respectively, all P < 0.001) . Flow cytometry showed that there was a significant difference in the apoptosis rate among the 4 groups (11.51% ± 1.84%, 23.83% ± 5.72%, 36.19% ± 8.33%, 49.75% ± 4.10%, respectively, F=17.62, P < 0.001) , and the 10-and 20-μmol/L groups showed significantly increased apoptosis rates compared with the control group ( t=4.46, 6.92 respectively, both P < 0.01) . Transcriptomics analysis revealed that the inhibitory effect of ECPIRM on the cellular proliferative activity may be related to the metabolic regulation of steroids. As reverse transcription-qPCR revealed, the 10-μmol/L ECPIRM group showed significantly decreased mRNA expression of L-amino acid oxidase (IL4I1) , acetyl-coenzyme A acetyltransferase 2 (ACAT2) , 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (HMGCS1) , mevalonate diphosphate decarboxylase (MVD) , 3-β-hydroxysteroid-8,7-isomerase (EBP) , very low-density lipoprotein receptor (VLDLR) , 3-hydroxy 3-methylglutaryl-CoA reductase (HMGCR) compared with the control group (all P < 0.05) . Conclusion:The retinoid derivative ECPIRM exerted marked anti-proliferative and apoptosis-inducing effects on HH cells, which may be related to the decreased expression of key genes involved in steroid metabolism.

目的 探讨阿达帕林对人皮肤T细胞淋巴瘤(CTCL)Hut78细胞增殖、凋亡及周期的影响.方法 采用CCK-8法检测不同浓度(0、0.01、0.1、1、2.5、5、10、25、50和100μmol/L)阿达帕林对人CTCL Hut78、Myla和HH细胞的增殖抑制作用,并分别计算IC50.采用膜联蛋白(Annexin)V/碘化丙啶(PI)双染法和PI单染法分别检测阿达帕林0、2、4和6 μmol/L对Hut78细胞凋亡和周期分布的影响,Western blot法检测阿达帕林对Hut78细胞DNA损伤标志蛋白γ-H2AX表达的影响.结果 阿达帕林对Hut78、Myla和HH细胞增殖的抑制作用具有浓度依赖性,Hut78细胞的IC50为(1.45±0.47)μmol/L,HH 细胞的 IC50为(2.89±0.22)μmol/L,Myla 细胞的 IC50为(30.51±2.12)μmol/L.与阿达帕林0 μmol/L组相比,阿达帕林2、4和6 μmol/L组Hut78细胞的凋亡率升高[(10.82±0.46)％、(55.51±2.88)％、(73.26±2.21)％vs.(5.79±0.90)％](P＜0.01),S 期细胞比例升高[(72.51±1.89)％、(69.84±1.89)％、(91.68±10.84)％vs.(45.99±0.48)％](P＜0.01),阿达帕林4和6μmol/L组细胞中γ-H2AX表达增加(P＜0.05).结论 阿达帕林可选择性抑制CTCL中Hut78细胞的增殖,并诱导Hut78细胞凋亡和S期阻滞,其机制可能与阿达帕林诱导的DNA损伤有关.

目的 研究奥美拉唑碳酸氢钠干混悬剂在健康人体的药代动力学和相对生物利用度,并以原研奥美拉唑碳酸氢钠干混悬剂为参比制剂,进行生物等效性评价.方法 用单中心、随机、两周期、两交叉、自身对照试验设计,分别入组40例受试者,Ⅰ组交叉口服受试制剂或参比制剂奥美拉唑碳酸氢钠干混悬剂20 mg,Ⅱ组交叉口服受试制剂或参比制剂奥美拉唑干混悬剂40 mg.用LC-MS/MS法测定血浆中奥美拉唑浓度,用WinNonlin 8.0计算药代动力学参数,并进行两种制剂的生物等效性评价.结果 受试者给予受试制剂及参比制剂奥美拉唑碳酸氢钠干混悬剂20 mg后Cmax分别为(869.85±366.05)和(858.38±370.23)ng·mL-1,AUC0-t分别为(1006.33±939.25)和(1022.64±1010.28)h·ng·mL-1.Cmax和AUC0-t的90％置信区间分别为92.93％ ～112.62％ 和95.50％～102.90％.受试者给予受试制剂及参比制剂奥美拉唑碳酸氢钠干混悬剂40 mg后Cmax分别为(2276.00±787.45)和(2162.92±793.21)ng·mL-1,AUC0-t分别为(3937.53±3336.61)和(3929.18±3034.03)h·ng·mL-1.Cmax和AUC0-t的90％置信区间分别为96.41％～117.74％和95.13％～103.49％.药代动力学参数个体间变异均超过25％.结论 受试制剂与参比制剂奥美拉唑碳酸氢钠干混悬剂20 mg和40 mg的药代动力学参数分别在80.00％ ～125.00％等效区间内,表明在中国健康受试者中具有生物等效性.

利伐沙班为临床上常用的抗凝药物,查阅文献,其不良反应未见有白细胞减少.本院开展的一项利伐沙班片在中国成年健康受试者中的一项生物等效性研究中,出现4例不同程度的白细胞减少(空腹受试者A,女性,29岁.餐后受试者B,男,22岁;C,女,29岁;D,女,23岁),并且在停药后白细胞水平恢复正常.故在临床使用利伐沙班时,加强对白细胞的监测.

Background and Objectives: Tissue engineering skin is a three-dimensional skin substitute cultured in the gas-liquid interface using the immortalized keratinocytes (HaCaT cells). In this study, the preliminary metabolism of betamethasone dipropionate by tissue engineering skin was studied and the pharmacokinetics methodology was established using betamethasone dipropionate gel as the target drug. Methods: The betamethasone dipropionate gel was applied on the tissue engineering skin after the skin was cultured. Then the medium (receiving liquid) and skin were taken on 0.25, 0.75, 1.75, 3, 5, 8, 12, 24, 36, 48 h time points. The betamethasone concentration in the medium and skin was determinated by the LC-MS method. Chromatographic analysis was conducted using isocratic elution on a C18 column (150 mm × 2.0 mm, 5 µm) in mobile phase consisting of methanol and water (70 : 30, v/v). The mobile phase was pumped at a flow rate of 0.2 mL/min. Results: This method exhibited linearity within the concentration range of 0. 1 to 50 µg /mL of betamethasone. The LLOQ was 0. 1 µg /mL. The intra- and inter-day precisions of betamethasone in the blank medium were all less than 10.69 % (RSD, %), while in the blank, skin homogenates were all less than 13.96 % (RSD, %). As a result, the betamethasone concentration in the medium and skin could both be detected, which suggested that betamethasone dipropionate could be metabolized to betamethasone through the tissue engineering skin. Conclusion: It was feasible to use tissue engineering skin as a model to study the dermatopharmacokinetics of topical betamethasone dipropionate gel. The research could build a foundation for the dermato-pharmacokinetic study approach.

黑色素瘤是一种源于黑色素细胞的恶性肿瘤,临床上约50％ 的黑色素瘤患者发生了BRAF突变.BRAF抑制剂能够作用于突变的BRAF位点,从而迅速对肿瘤细胞发挥增殖抑制和促进凋亡作用,但此后迅速发生的耐药事件严重制约了该类药物的连续使用,所以对于BRAF抑制剂耐药机制的探究非常重要.本文介绍了近年来有关黑色素瘤BRAF抑制剂耐药的相关研究进展,以期为后续的相关研究和临床应用提供一定的参考.

Pharmacogenetics and pharmacometabolomics are the common methods for personalized medicine, either genetic or metabolic biomarkers have limited predictive power for drug response. In order to better predict drug response, the study attempted to integrate genetic and metabolic biomarkers for drug pharmacokinetics prediction. The study chose celecoxib as study object, the pharmacokinetic behavior of celecoxib was assessed in 48 healthy volunteers based on UPLC–MS/MS platform, and celecoxib related single nucleotide polymorphisms (SNPs) were also detected. Three mathematic models were constructed for celecoxib pharmacokinetics prediction, the first one was mainly based on celecoxib-related SNPs; the second was based on the metabolites selected from a pharmacometabolomic analysis by using GC–MS/MS method, the last model was based on the combination of the celecoxib-related SNPs and metabolites above. The result proved that the last model showed an improved prediction power, the integration model could explain 71.0% AUC variation and predict 62.3% AUC variation. To facilitate clinical application, ten potential celecoxib-related biomarkers were further screened, which could explain 68.3% and predict 54.6% AUC variation, the predicted AUC was well correlated with the measured values (r = 0.838). This study provides a new route for personalized medicine, the integration of genetic and metabolic biomarkers can predict drug response with a higher accuracy.

Sepiapterin reductase plays an enzymatic role in the biosynthesis of tetrahydrobiopterin, which is reported in limited studies to regulate the progression of several tumors. However, the role of sepiapterin reductase in hepatocellular carcinoma remains largely unknown. Here, we found that sepiapterin reductase was frequently highly expressed in human hepatocellular carcinoma, which was significantly associated with higher T stage, higher tumor node metastasis stage, and even shorter survival of hepatocellular carcinoma patients. Furthermore, cell and animal experiments showed that sepiapterin reductase depletion inhibited cancer cell proliferation and promoted cancer cell apoptosis. Importantly, the results suggested that sepiapterin reductase enzymatic activity was not necessary for the progression of hepatocellular carcinoma, based on the comparison between SMMC-7721 and SMMC-7721 containing sepiapterin reductase mutant. Moreover, we showed that sepiapterin reductase regulated the development of hepatocellular carcinoma via the FoxO3a/Bim-signaling pathway. Collectively, our study suggests that sepiapterin reductase controls hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner, which provides a potential prognostic factor and therapeutic strategy for hepatocellular carcinoma.

BackgroundThe treatment of Cutaneous T-cell lymphoma (CTCL) met huge challenges because of the heterogeneity and the scarcity of targeted drugs. ECPIRM derived from isotretinoin exhibited strong anti-proliferation effects in Hut78 and MJ cells rather than Myla cells. However, there was no data regarding the potential target of ECPIRM for its selective activity.ObjectivesTo investigate the potential target of ECPIRM for its selective anti-proliferation activity.MethodsWe evaluated the cell viability of CTCL cells after ECPIRM treatment, and detected the effects of ECPIRM on the biomarker genes of CTCL. Subsequently, the mRNA and protein level of Interleukin-2-inducible T-cell kinase (ITK) was determined. Then the induction of apoptosis triggered by ITK inhibitor BMS-509744 and ITK siRNAs were detected, and the docking of ECPIRM interacted with ITK and the effects of ECPIRM on ITK-mediated signaling pathway were analyzed. Finally, we evaluated the anti-growth activity of ECPIRM in Hut78-xenografted nude mice, and the relative expression of cleaved caspase-3, ITK, p-ERK and p-Akt were determined.ResultsITK was highly expressed in Hut78 and MJ cells rather than Myla cells, and targeted inhibition of ITK triggered cell apoptosis. ECPIRM efficiently bound the hydrophobic active pocket of ITK, and significantly inhibited ITK-mediated signaling pathway. In addition, ECPIRM suppressed tumor growth in Hut78-xenografted model, and upregulated the expression of cleaved caspase 3 and inhibited the expression of ITK, p-ERK and p-Akt in tumor tissues, which was consistent with in vitro study.ConclusionECPIRM might provide a novel strategy for CTCL by inhibiting ITK-mediated signaling pathway.

BACKGROUND:The combination of ketoconazole and dexamethasone acetate is one of the commonly used treatments in dermatology regiment for skin inflammation accompanied by fungal infections. This interaction of ketoconazole and dexamethasone may make the drug much effective, decrease the adverse reaction or toxic effects. At present, there was no information about the interaction of these two external drugs. Therefore, it was necessary to build a model to measure the levels and evaluate the interaction of ketoconazole and dexamethasone acetate in skin cells. METHODS:In our study, the determination methodology of ketoconazole and dexamethasone acetate in human keratinocyte (HaCaT cells) was established and the interaction of these two drugs in cells was explored. HaCaT cells were cultured in medium containing ketoconazole, then they were sequentially cultured with or without dexamethasone acetate treatment for another 1, 2, 4, 8 and 12 h. The samples were then harvested and the concentrations were quantified by enhanced BCA (the bicinchoninic acid) protein assay. Furthermore, the analytes in the cell suspension were also prepared and analyzed by LC-MS method. RESULTS:As a result, ketoconazole and dexamethasone acetate were detected at the concentration range of 0.02 to 5 μg/mL and 0.2 to 100 μg/mL, respectively. The RSD (relative standard deviation) and RE (relative error) of precision and accuracy of the two analytes in the cell suspension were all less than 15 %. The matrix effect values variations were all less than 15%. The results showed that there was no significant difference in the concentration of ketoconazole with or without dexamethasone acetate treatment within 12 h. CONCLUSIONS:A simple, sensitive and rapid LC-MS method which could quantify these two analytes in cells simultaneously was developed for the first time. The results of the concentration changes meant that no interaction occurred when dexamethasone sequentially administrated for 12 h after ketoconazole treatment. This method was successfully applied to establish the cell pharmacokinetics methodology and preliminary studied the metabolism of drug-drug interaction of ketoconazole and dexamethasone acetate.

The vitamin A derivative 9-cis-retinoic acid (9-cis-RA) has been used for the treatment and prevention of cutaneous T-cell lymphoma (CTCL). However, the precise mechanism by which 9-cis-RA treatment ameliorates CTCL remains elusive. Our research shows that 9-cis-RA inhibits proliferation and induces apoptosis in CTCL cells in a dose-dependent and time-dependent manner. 9-Cis-RA also induced G0/G1 cell cycle arrest by downregulation of cyclin D1. We confirmed that 9-cis-RA significantly decreased phosphorylation of JAK1, STAT3, and STAT5 and downregulated Bcl-xL and cyclin D1, indicating that 9-cis-RA inhibited the activation of JAK/STAT signaling. Meanwhile, 9-cis-RA also activated classical RA-mediated transcription by retinoic acid receptors (RAR) and/or retinoid X receptors (RXR) in a CTCL cell line. Thus, 9-cis-RA may be effective for chemotherapy and may prevent human CTCL by inhibiting proliferation and inducing apoptosis by inhibition of the JAK/STAT pathway and activation of the RAR/RXR pathway.