Metformin partially reverses the carboplatin-resistance in NSCLC by inhibiting glucose metabolism.

Platinum-based chemotherapeutic drugs are irreplaceable for the treatment of advanced non-small cell lung cancer (NSCLC). However, acquired drug resistance has become a major obstacle for the clinical application of chemotherapy on NSCLC. In the present study, we established carboplatin-resistant NSCLC models on A549 and PC9 cell lines, which were named A549/R and PC9/R. Besides the low sensitivity of A549/R and PC9/R to carboplatin treatment, they exhibited higher metabolism rate of glucose compared to their parental A549 and PC9 cells, respectively. Mechanically, we confirmed that overexpression of PKM2 in A549/R and PC9/R was responsible for the high glucose metabolism and carboplatin resistance. Metformin, an antidiabetic drug, was observed to increase the sensitivity of carboplatin-resistant NSCLC cells to carboplatin treatment