Therapeutic Efficacy Of Xiaotan Sanjie Formula On Microsatellite Instability Of Human Gastric Cancer Mkn-45 Cells And Exploration Of The Underlying Mechanism

Objective: To evaluate the therapeutic efficacy and explore the action mechanism of Xiaotan Sanjie Formula (XSF) on microsatellite instability (MSI) in human gastric cancer MKN-45 cells. Methods: The therapeutic efficacy of XSF on human gastric cancer MKN-45 cell proliferation was detected by CCK-8. Five MSI loci (D17S250, D2S123, D5S346, Bat-25 and Bat-26) were detected by STR Genotyping. The effect of XSF on the expression of MSI proteins of hMLH1, TGF beta RII, IGFRII and Bax was analyzed by Western blot and RT-PCR. Results: XSF inhibited the proliferation of human gastric cancer MKN-45 cells in a time-dependent manner. When these MKN-45 cells were amplified to the five MSI loci, both D2S123 and D5S346 showed MSI with two peaks. After 48-h intervention with XSF, the mutation of D2S123 and D5S346 loci tended to be stabilized; the relative expression level of hMLH1, TGF beta RII and Bax mRNA was increased in varying degrees, and the expression level of IGFRII mRNA tended to decrease, while the expression level of IGFRII protein was increased significantly (P<0.05). Conclusion: XSF inhibited MSI of human gastric cancer MKN-45 cells, probably by up-regulating MSI-associated hMLH1, TGF beta RII, IGFRII and Bax gene and protein expressions, and IGFRII protein expression.