The Mismatch Repair Gene HMLH1Is Associated With Apoptosis Induced By Estrogen In Colorectal Cancer Cell Line HCT116

INTRODUCTION:Colorectal cancer (CRC) is a common malignancy with a high death rate. A study which use HNPCC family members as the research object thought that regarding to the risk of colon cancer, the male mutation carriers is much higher than female mutation carriers. Epidemiological data indicate that estrogen (E2) may be beneficial for the prevention of colorectal cancer. Several studies of antiproliferative and proapoptotic effects in the colorectal cancer induced by the activation of the estrogen recepter β (ERβ) have been reported. The largest number of mutations has been detected in the mismatch repair (MMR) genes hMLHl and hMSH2. Recent work has implicated that estrogen induces the up-regultion of hMLHl activity but not hMSH2in vitro, and high serum estrogen level correlates with hMLHl expression in vivo. Furthermore, hMLHl may involved in colorectal cancer cell apoptosis induced by a variety of DNA damage medium (cisplatin, alkylating agents,5-fluorouracil etc.). Howerver, it is unknown whether the apoptosis induced by estrogen correlates with hMIHl in colorectal cancer.AIM:To investigate the role of hMLHl on the estrogen-induced apoptosis in colorectal cancer cell HCT116.MATERIALSAND METHODS:In this study, hMLHl gene was constructed into pcmv vector and forcibly expressed in HCT116(a cell line with hMLHl mutation). The transfection effect was verified by western blot. Different concentrations of estrogen were used after stable expression. Then the apoptosis rate was examined using flow cytometry, DAPI staining, western blot and cell counting kit-8techniques respectively.RESULTS:The hMLHl function in HCT116was successfully restored by transfection compared with no-load group. The treatment of estrogen (10-8mol/L) in hMLHl-HCT116decreased the cell activity. The significant apoptosis enhancement was observed. In agreement with increased apoptosis, caspase3/9break was also occurred in hMLHl group compared with control group obviously.CONCLUSIONS:hMLHl is involved in estrogen-induced apoptosis in colorectal cancer cell line HCT116.