Norcantharidin (NCTD) is a demethylated derivative of cantharidin, which is an anticancer active ingredient of traditional Chinese medicine, and is currently used clinically as a routine anti-cancer drug in China. Clarifying the anticancer effect and molecular mechanism of NCTD is critical for its clinical application. Here, we summarized the physiological, chemical, pharmacokinetic characteristics and clinical applications of NCTD. Besides, we mainly focus on its potential multi-target anticancer activities and underlying mechanisms, and discuss the problems existing in clinical application and scientific research of NCTD, so as to provide a potential anticancer therapeutic agent for human malignant tumors.

Objective To investigate the expression of ubiquitin-conjugating enzyme E2s (UBE2S) in gallbladder cancer (GBC) tissues and its clinical significance.Methods The expression of UBE2S was examined in 85 GBC,28 pre-malignant lesion and 15 benign lesion tissues of the gallbladder by immunohistochemistry,and was verified by western blotting.The relationship between UBE2S expression and clinicopathological characteristics and prognostic factors of GBC patients was analyzed.Results Immunohistochemistry showed that UBE2S was highly expressed in GBC tissues compared to pre-malignant lesion tissues [stain index (SI):4.082 ± 3.413 vs.2.607 ± 2.025,P =0.021)] and benign lesion tissues (SI:4.082 ± 3.413 vs.2.067 ± 1.335,P =0.001),and western blotting showed that UBE2S protein was highly expressed in GBC tissues compared to benign lesion tissues (grey-scale value:0.734 ±0.181 vs.0.197 ± 0.099,P =0.002).UBE2S was positively correlated with tumor differentiation degree (x2 =6.978,P =0.031) and liver metastasis (x2 =8.155,P =0.004).Cox model showed that UBE2S expression (P =0.024) as well as tumor differentiation degree (P =0.000),Nevin stage (P =0.040) and R0 resection (P =0.011) were prognostic factors of GBC patients.High UBE2S expression patients with GBC have a shorter survival time (P =0.011).Conclusion High UBE2S expression is an independent factor of unfavorable prognosis in GBC patients.

Human gallbladder cancer (GBC) is a lethal aggressive malignant neoplasm. Identification of potential molecular biomarkers and development of targeted therapeutics for GBC patients is very necessary. In this study, we firstly investigated the correlation between ring finger protein 125 (RNF125) expression and the metastasis and prognosis of GBC, and the underlying molecular mechanism. RNF125 expression in a cohort of GBC tissues was examined; its correlation with clinicopathological and prognostic factors of GBC patients was analyzed. Moreover, the metastasis-related difference expressed genes in highly and lowly aggressive GBC cell lines were identified; and the influence of RNF125 knockdown on the metastatic phenotypes and characteristic EMT markers in highly aggressive GBC NOZ cells was detected. Furthermore, the underlying molecular mechanism of RNF125 effect was explored. The results showed that RNF125 was highly expressed in GBC tissues and related with aggressive characteristics such as Nevin stage (P = 0.041) etc. and unfavorable prognosis of GBC patients (P = 0.023, log-rank test). And, RNF125 was proved to a positive metastasis-related gene in vitro. RNF125 knockdown inhibited the invasion and migration, enhanced the adhesion, upregulated E-cadherin and β-catenin expression, and downregulated vimentin and N-cadherin expression (all P < 0.001) of NOZ cells in vitro. RNF125 promoting effect on GBC tumor progression was identified to relate with the activation of TGF-β1-SMAD3-ID1 signaling pathway. These findings firstly confirm that high RNF125 expression is related with aggressive characteristics and unfavorable prognosis of GBC patients; RNF125 promotes the invasion and metastasis of human GBCs via activating the TGF-β1-SMAD3-ID1 signaling pathway.

This paper reviews the source,structure and function of the cell fate determination factor 1(Dachshund homologue 1,DACH1),and roles in growth of malignant tumors and their regulation mechanisms,in order to explore DACH1 as a target for targeting diagnosis and adjuvant therapy of malignant tumors.