OBJECTIVE: To investigate the role of metformin on the growth inhibition induced by chemotherapeutic agents in hypopharyngeal carcinoma Fadu cells.METHODS: Fadu cells were treated with different concentrations of metformin for different time or treated with different concentrations of cisplatin, 5-fluorouracil or paclitaxel with or without metformin 5 mmol/L. MTT assay was used to evaluate the influence of metformin on the proliferation of Fadu cells. Cell-cycle was analyzed by flow cytometry. The expressions of AMP-dependent/activated protein kinase (AMPK) and P21 were examined by immunocytochemistry.RESULTS: Metformin inhibited the proliferation of Fadu cells in a dose-and time-dependent manner.Flow cytometry showed that cell cycle arrest in G1 phase was induced by metformin in Fadu cells.Immunocytochemistry showed the expressions of both AMPK and P21 in cells treated with metformin were higher than those in cells untreated with metformin. The growth inhibition of cells induced by cisplatin or paclitaxel but not 5-fluorouracil was enhanced by metformin. The combined indexes of cisplatin/paclitaxel/5-fluorouracil and metformin for 48 h were 0.43, 0.37, and 1.15, respectively.CONCLUSIONS: Metformin may inhibit the proliferation of Fadu cells by inducing the cell cycle arrest in G1 phase mediated in part by AMPK and P21. Metformin enhances the sensitivity of Fadu cells to cisplatin and paclitaxel.
AMP-Activated Protein Kinases Antineoplastic Agents