Proliferation And Apoptosis Of Metformin On Esophageal Cancer KYSE450 Cells And The Possible Mechanisms

Background and objectives: Esophageal cancer is one of the world’s common malignant tumor in our country, the incidence and mortality of up to first in the world, the onset of world standard rate of sixth, the death rate is the twelfth world standard.Early esophageal cancer symptom is slight, when the clinical manifest ationsand medical treatment, most have been at the late, lost the operation treatment opportunities, while chemotherapy as one of the important means of treatment of esophageal cancer. But the chemotherapy drug adverse reaction is currently poor tolerance, and prone to resistance. For treatment of esophageal carcinoma is the hotpot in the field of new effective drugs. Research shows that metformin can inhibit colon cancer, breast cancer, liver cancer and glioma tumor cells growth, Kobayashi research showed that metformin can inhibit TT, KYSE30 and KYSE70 3 kinds of esophageal cancer cell proliferation. By different concentration of metformin in esophageal cancer cell KYSE450 study aimed to the experiment and observe its inhibitory effect on the proliferation of esophageal cancer cells, and to explore the possible mechanism.Methods: KYSE450 cells were cultured in vitro. The effect of cell proliferation and apoptosis were detected by MTT assay and flow cytometer(FCM), respectively.The m RNA and protein expressions levels of 4EBP1 and S6K1 were detected by Western bolt and RT-PCR.Results: 1. Different concentrations of metformin could obviously inhibit the proliferation of KYSE-450 in a dose-dependent and time-dependent manners(P<0.05),And the proliferation inhibition rate of KYSE-450 was significantly higher than control group in a dose-dependent and time-dependent manners(P<0.05). 2.Cell apoptosis was detected by flow cytometry in each experimental group:the experimental group of different concentrations of metformin apoptosis rate was(20.8±1.35)%、(30.1±1.56)%、(39.7±1.44)%.control group rate was significantly lower than in control group(P<0.05). 3. PCR assay the 4EBP1,S6K1 molecules m RNA expression of each experimental group were significantly higher than control group(P<0.05). 4.Western-blot assay the 4EBP1,S6K1 molecules m RNA expression of each experimental group were significantly higher than control group(P<0.05).Conclusion : 1.Metformin can inhibit the proliferation and induce apoptosis of esophageal cancer KYSE450 cells in vitro, 2.Probably by down-regulating the expressions of 4EBP1 and S6K1.