A novel therapy for lung cancer targeting cancer stem cells.

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Cytotoxicity of metformin was elucidated in 4 human lung cancer cell lines. Colonogenicity and cell proliferation were inhibited by metformin in all the cell lines only when the cells were exposed to the metformin for a long period, suggesting its cytostatic characteristics. The combined effects of metformin and gefitinib were examined. It did not suppress the growth of already established tumors, nor did it augment tumor shrinkage by gefitinib. However, it significantly suppressed the regrowth of the tumor after effective treatment with gefitinib, suggesting metformin's specific effect on the residual cells. Its cytotoxicity was characterized by the absence of apoptosis induction and unremarkable cell cycle shift. The residual cells were characterized by enriched cells with high expression of CD133 and CD24. Metformin was still effective on this specific cell population. Targeting residual cells after chemotherapy might represent an effective new strategy for curing cancer.