Background: JianPiTongLuo Recipe (JPTL Recipe) is a traditional Chinese medicine formula commonly used in the clinical treatment of colorectal cancer. Clinical studies have found that it can significantly improve the prognosis of patients with colorectal cancer. However, its mechanisms of action are not well understood, which has limited its further clinical application. Methods: We investigated the potential mechanisms of action of the JianPiTongLuo (JPTL) Recipe on colorectal cancer (CRC) using a multi-step approach. Initially, network pharmacology and bioinformatics analyses were conducted using databases such as TCMSP, HERB, BATMAN-TCM, and STRING to identify active components of JPTL Recipe and predict their therapeutic targets. Interaction networks and functional enrichment analyses were constructed to hypothesize relevant biological processes and pathways. In vitro studies involved treating human CRC cell lines HCT116, LoVo and SW480 with varying concentrations of JPTL Recipe extract, measuring cell viability with the CCK-8 assay, assessing apoptosis via flow cytometry, and analyzing signaling pathways through Western blotting. To corroborate these findings, in vivo experiments were performed on BALB/c nude mice implanted with HCT116 cells, divided into control, JPTL Recipe- treated, 5-fluorouracil (5-FU)-treated, and JPTL Recipe combined with 5-FU groups, with tumor growth and histological changes monitored. Mechanistic studies focused on the PI3K/AKT signaling pathway, examining the phosphorylation status of key pathway proteins using immunofluorescence and Western blot analyses to elucidate JPTL Recipe 's interaction with pathway activity. Results: We demonstrated that JPTL Recipe effectively inhibits colorectal cancer cell proliferation, anti-apoptotic ability, and exerts synergistic therapeutic effects with fluorouracil. Further analysis revealed that JPTL Recipe affects the activity of colorectal cancer cells by inhibiting the phosphorylation of the PI3K/AKT signaling pathway. Conclusion: In summary, we have discovered and confirmed that the traditional Chinese medicine compound JPTL Recipe can serve as a novel adjuvant therapy for colorectal cancer, offering a new treatment approach for the integration of traditional Chinese and Western medicine in the treatment of colorectal cancer.

Background:Colorectal cancer (CRC) is an insidious malignancy and the occurrence of chemotherapy resistance and toxicity seriously limits its clinical efficacy. Insect Compound Particle [Chong Yao Fu Fang (CYFF)] is a traditional Chinese medicine (TCM) compound based on the concepts of "invigorating spleen for strengthening vital qi" and "collateral disease theory". In long-term clinical application, it can reduce the toxicity of CRC chemotherapy and improve the anti-tumor effect. However, there is currently a lack of high-quality clinical evidence to prove the clinical efficacy and safety of CYFF in the treatment of CRC. Methods:We plan to include 262 patients with locally advanced stage III CRC who had undergone surgery and achieved R0 resection. These patients will be randomized into a CYFF group (treated with CYFF combined with chemotherapy) and a control group (treated with placebo plus chemotherapy) at a 1:1 ratio. The patients were routinely followed-up every 2 weeks within 2 months and every 4 weeks after 2 months after the treatment, every 3 months within 1 year, and every 6 months after 1 year. The primary endpoint is disease-free survival (DFS), defined as the time from random assignment to recurrence of primary CRC or death from any cause. The secondary endpoints include overall survival (OS) (defined as the time from randomization to death from any cause), safety [any adverse events (AEs)], and the Colorectal Cancer-Specific Quality of Life Questionnaire (QLQ-CR38) score. Conclusions:Compared with previous studies, our current study applies CYFF plus basic adjuvant chemotherapy, which is expected to achieve better efficacy and longer survival than standard chemotherapy, and reduce the toxic and side effects of chemotherapy, improve the safety of clinical treatment. In addition, our present study is the first clinical study to evaluate the safety and efficacy of CYFF in combination with chemotherapy in the treatment of stage III CRC after R0 resection. Trial Registration:This clinical trial has been registered in the Chinese Clinical Trial Registry (ChiCTR) (registration No. ChiCTR2000037568; August 28, 2020).

目的 探究健脾通络方对结直肠癌细胞侵袭、迁移的影响及机制.方法 构建敲减MALAT1基因的HCT116细胞模型.采用细胞划痕实验和Transwell实验检测细胞侵袭、迁移能力.采用蛋白质印迹法检测经健脾通络方干预后的MALAT1正常/敲减表达的HCT116细胞中Wnt3a、β-catenin蛋白水平.采用实时荧光定量PCR法检测MALAT1的表达水平.构建裸鼠肺转移模型,采用小动物活体成像技术监测肿瘤转移情况,并检测转移灶中Wnt3a、β-catenin和MALAT1的表达水平.结果 经健脾通络方干预后,HCT116细胞中MALAT1、Wnt3a和β-catenin的表达水平均降低,HCT116细胞迁移能力下降.在裸鼠肺转移模型中,经健脾通络方干预后裸鼠的转移灶减少,转移灶中Wnt3a、β-catenin和MALAT1的表达水平均降低.结论 健脾通络方通过下调HCT116细胞中MALAT1的表达,使Wnt/β-catenin信号通路中Wnt3a、β-catenin的蛋白表达水平降低,从而抑制结直肠癌细胞的增殖、侵袭和迁移能力.

消化系统肿瘤是中国常见的恶性肿瘤,由于目前治疗方法存在局限性,研究方向从单纯研究肿瘤细胞内部机制延伸至研究肿瘤微环境中的外泌体与免疫细胞之间的作用和关系.消化系统肿瘤微环境中的外泌体可以通过传递信号抑制免疫细胞的杀伤能力,促进肿瘤的发生、发展.肿瘤细胞通过释放外泌体传递信息,诱导巨噬细胞极化,抑制免疫细胞活性,促进肿瘤转移及免疫逃逸.该文综述了消化系统肿瘤源性外泌体在肿瘤微环境中对免疫细胞作用的研究进展.