ABSTRACT
OBJECTIVE@#Xiaotan Sanjie recipe (XTSJ), a Chinese herbal compound medicine, exerts a significant inhibitory effect on gastric cancer (GC) metastasis. This work investigated the mechanism underlying the XTSJ-mediated inhibition of GC metastasis.@*METHODS@#The effect of XTSJ on GC metastasis and the associated mechanism were investigated in vitro, using GC cell lines, and in vivo, using a GC mouse model, by focusing on the expression of Glc-N-Ac-transferase V (GnT-V; encoded by MGAT5).@*RESULTS@#The migration and invasion ability of GC cells decreased significantly after XTSJ administration, which confirmed the efficacy of XTSJ in treating GC in vitro. XTSJ increased the accumulation of E-cadherin at junctions between GC cells, which was reversed by MGAT5 overexpression. XTSJ administration and MGAT5 knockdown alleviated the structural abnormality of the cell-cell junctions, while MGAT5 overexpression had the opposite effect. MGAT5 knockdown and XTSJ treatment also significantly increased the accumulation of proteins associated with the E-cadherin-mediated adherens junction complex. Furthermore, the expression of MGAT5 was significantly lower in the lungs of BGC-823-MGAT5 + XTSJ mice than in those of BGC-823-MGAT5 + solvent mice, indicating that the ability of gastric tumors to metastasize to the lung was decreased in vivo following XTSJ treatment.@*CONCLUSION@#XTSJ prevented GC metastasis by inhibiting the GnT-V-mediated E-cadherin glycosylation and promoting the E-cadherin accumulation at cell-cell junctions. Please cite this article as: Huang N, He HW, He YY, Gu W, Xu MJ, Liu L. Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation. J Integr Med. 2023; 21(6): 561-574.
Subject(s)
Male , Mice , Animals , Stomach Neoplasms/genetics , Drugs, Chinese Herbal/pharmacology , Glycosylation , Cell Line, Tumor , Cadherins/metabolismABSTRACT
Objective: To screen the different mutated somatic genes between primary ovarian cancer and metastatic ovarian carcinoma using the whole exon sequencing data of catalogue of somatic mutations in cancer (COSMIC) database, and to analyze their function and signal pathway. Methods: The whole exon sequencing data of all tumors were downloaded from the COSMIC database, and the whole exon sequencing data of all ovarian cancer were extracted. In the R 3.5.3 environment, mutation rate of each mutated gene in the primary and metastatic ovarian carcinoma samples were performed. The χ2 test or Fisher's exact probability method was used to identify the mutated gene groups which had statistically significant difference in mutation rate. The mutated gene groups were further analyzed for gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment. Results: We found a total of 520 somatic mutations with statistically significant differences in mutation rate between primary ovarian cancer and metastatic ovarian carcinoma tissues, such as transmembrane protease serine 13 (TMPRSS13), Golgi brefeldin A resistance factor 1 (GBF1), Fos-like antigen 2 (FOSL2), mastermind-like 3 (MAML3), etc. Enriched GO function included presynapse organization, dendrite development, cell-cell adhesion via plasma membrane adhesion molecules, and actin binding, and so on. KEGG pathway included regulation of actin cytoskeleton, tricarboxylic acid carrier, and the like. Conclusion: It can provide clues for revealing the metastasis regulation mechanism of ovarian cancer by exploring different mutated gene group between primary ovarian cancer and metastatic ovarian carcinoma and its related functional pathways. The significant mutated gene group may be used as biomarkers for the diagnosis and treatment of ovarian metastatic cancer.
ABSTRACT
Cervical cancer is the second most commonly seen cancer in women and the third leading cause of cancer death in developing countries. Early diagnosis and treatment are the keys to the effective treatment of cervical cancer and the improvement of prognosis. Because of the complexity, the mechanism of development and progression of cervical cancer is still an urgent problem to solve. Recently, quantity of studies have shown that long non-coding RNAs (lncRNAs) play important roles in tumor development and progression. In this review, we sumed up the multiple effects of lncRNAs in cervical cancer, focusing on the related mechanisms of human papilloma virus (HPV) E6 and E7 oncoprotein, the nature of lncRNAs and the signaling pathway in the development and progression of cervical cancer. And we further expounded the cervical cancer mechanism network, providing reference for screening the potential markers for early diagnosis and treatment of cervical cancer.