[Metformin's effect on 5-fluorouracil,cisplatin,paclitaxel in laryngocarcinoma Hep-2 cells]

Abstract

Objective:To investigate metformin's effect on chemosensitivity of chemotherapeutic drug 5-fluorouracil in laryngocarcinoma Hep-2 cells. Investigate the variation trend of protein expression of AMPK pathway in the combined effect.Method:Laryngocarcinoma Hep-2 cells were treated with different concentrations of 5-fluorouracil in vitro together with or without metformin for 72 h. Use MTT assay to investigate the influence on the inhibition rate to Hep-2 cells. Hep-2 cells were treated with cisplatin, 5-fluorouracil or paclitaxel with or without metformin. Use Western blot assay to investigate the expression level of AMPKα, P21 or Cyclin D1 protein. Result:5-fluorouracil and metformin could inhibit the proliferation of Hep-2 cells. 5-fluorouracil in low concentration combined with metformin could increase the proliferation inhibition rate of Hep-2 cells. In the circumstances of using 5-fluorouracil in high concentration with metformin , the cell proliferation inhibition rate of combining group makes no differences with the single-drug group. The combination of metformin and 5-fluorouracil produced an antagonism action in Hep-2 cells.Western blot assay showed that metformin, cisplatin, 5-fluorouracil could have caused the increase of expression level of AMPK-α, P21 and Cyclin D1 in Hep-2 cells while Paclitaxel could have cause the decrease of expression level of Cyclin D1. Using combined drug could cause the change of protein expression. Conclusion:5-fluorouracil has been found to inhibit the proliferation of Hep-2 cells. Metformin has an antagonism on the anticancer effect to 5-fluorouracil in Hep-2 cells, and this antagonistic effect occurred partially through molecular signal pathways of AMPK-α, P21 and Cyclin D1 and it's significantly related to the cell cycle arrest.

Keywords: AMPK; Cyclin D1; P21; laryngeal neoplasms; metformin.