通关藤苷G对胃癌细胞增殖、转移和凋亡的影响及其机制OA

Objective To investigate the effects of Tenacissoside G on the proliferation,migration,invasion,and apop-tosis of gastric cancer cells and to elucidate its underlying mechanism.Methods Human gastric cancer MGC803 cells were ran-domly assigned to groups A-D.Group A cells were cultured under normal conditions without intervention;group B cells were treated with Tenacissoside G;group C cells were treated with Tenacissoside G and infected with an adeno-associated virus empty vector(AAV-NC);group D cells were treated with Tenacissoside G and infected with an overexpression AAV vector carrying the Ras homolog family member A(RhoA)gene.Cell viability,migration rate,invasion number,and apoptosis rate were measured using the MTT assay,wound-healing assay,Transwell assay,and flow cytometry,respectively.Specific pathogen-free 6-week-old BALB/c-nu nude mice were assigned to groups Ⅰ-Ⅳ.MGC803 cells were injected subcutaneously into the right axilla of each mouse.Mice in group Ⅱ received intraperitoneal injections of Tenacissoside G-saline solution every other day;mice in groups Ⅲ and Ⅳ received intraperitoneal injections of Tenacissoside G-saline solution and tail vein injections of AAV-NC and AAV-RhoA,re-spectively;mice in group Ⅰ received equal doses of saline every other day by intraperitoneal and tail vein injections.On day 21 after tumor establishment,tumor tissues were harvested,and the proportions of PCNA-positive and TUNEL-positive cells were as-sessed by immunohistochemistry and TUNEL staining,respectively.The expression levels of proteins related to the RhoA/Rho-as-sociated coiled-coil forming kinase(ROCK)signaling pathway in the cells and tumor tissues were measured by Western blotting.Results Compared with group A,group B cells showed signi-ficantly reduced cell viability,migration rate,invasion number,and relative expression levels of RhoA,ROCK1,and ROCK2 proteins,while the apoptosis rate was significantly increased.Compared with group C,group D cells showed significantly increased cell viability,migration rate,invasion number,and relative expression levels of RhoA,ROCK1,and ROCK2 proteins,while the apoptosis rate was significantly decreased(F=49.06-968.01,q=11.25-54.95,P＜0.05).Compared with group Ⅰ,tumor tissues from group Ⅱ mice showed significantly decreased proportion of PCNA-positive cells and relative expression levels of RhoA,ROCK1,and ROCK2 proteins,while the proportion of TUNEL-positive cells was significantly increased.Compared with group Ⅲ,tumor tissues from group Ⅳ mice showed significantly increased proportion of PCNA-positive cells and relative expression levels of RhoA,ROCK1 and ROCK2 proteins,while the proportion of TUNEL-po-sitive cells was significantly decreased(F=47.20-397.34,q=11.78-34.59,P＜0.05).Conclusion Tenacissoside G may exert an anti-gastric cancer effect by downregulating the expression of proteins in the RhoA/ROCK signaling pathway,thereby inhibiting the proliferation,migration,and invasion of gastric cancer cells and promoting their apoptosis.