Effects of p27 and HIF-1α on Metformin Impacting Proliferation and Apoptosis of Hypopharyngeal Carcinoma Cells

SHAN Shan; LI Xiao-ming; ZHOU Chen-yang; MIAO Yu-hua

doi:10.3969/j.issn.1002-3429.2017.04.034

Abstract：Objective To investigate the effects of metformin on cell proliferation and apoptosis in human hypopharyngeal carcinoma cells in vitro and in vivo, and to observe the mechanism of p27 and hypoxia inducible factor-1α(HIF-1α) in above, we can explore the theoretical basis of metformin for the clinical treatment.Methods Fadu cells in vitro were treated with different concentrations(0、5、10 mmol/L) metformin for 24 h, and with 5 mmol/L medicine for 48 h, to examine the expressions of p27 and HIF-1α by immunocytochemistry.The hypopharyngeal carcinoma xenografts in nude mice model were randomized into control group, low-dose metformin treatment group (met 40 group, daily 40 mg/kg) and high-dose metformin treatment group (met 200 group, daily 200 mg/kg).28 days treatment by intraperitoneal injection later, we collect the tumor, measure their volume, calculate tumor inhibition ratio and observe the tumor morphology by HE.Then the tumors were used for immunohistochemical analyses to detect p27 and HIF-1α.Results Compared with the control group, the expressions of p27 were higher in the hypopharyngeal carcinoma cell in vitro by metformin dose-and-time dependent (P<0.05), nevertheless, the expressions of HIF-1αwere lower(P<0.05).The average volumes of hypopharyngeal carcinoma xenografts of the two metformin treated groups were significantly low compared with that of the control group.And the expressions of p27 were higher and of the HIF-1α were lower than those in cells untreated with metformin(P<0.05).Conclusion Metformin can inhibit the growth and promote apoptosis of hypopharyngeal carcinoma cell in vitro and in vivo effectively, to provide the basis for the clinical treatment of hypopharyngeal carcinoma.