AB060. Could glucose uptake ability enhanced by drugs result in antitumor effect in small cell lung cancer?

Background: Lung cancer is still the leading cause of cancer-related deaths worldwide and novel therapeutic approaches are urgently needed for efficient therapies. Metformin and pioglitazone are approved medications for type 2 diabetes. Recent studies indicate that these anti-diabetic agents may inhibit the growth of some cancer cells but the mechanism(s) remain unclear. Another promising anti-cancer agent includes dichloro acetate (DCA). The present study aimed to investigate the inhibitory effect of these drugs on the proliferation of small cell lung cancer cell line via the investigation of the glucose uptake ability in cells.

Methods: Metformin, pioglitazone and DCA are the agents that were combined with the chemotherapeutic drugs (cisplatin, docetaxel and etoposide). Lung cancer cell line (NCI-H1048-Small cell lung cancer) was purchased from ATCC LGC Standards. Glucose uptake ability was evaluated by fluorescent d-glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG) followed by flow cytometric detection of fluorescence produced by the cells. At indicated time-point, following 24 h incubation, cell viability and apoptosis were measured with Annexin V staining by flow cytometry. Statistical analysis was performed by GraphPad Prism.

Results: In small cell lung cancer cells, following 24 h incubation, combinations of metformin and insulin, pioglitazone and insulin, DCA and insulin, resulted in increased amount of glucose uptake combined with increased apoptosis (P<0.0001). When chemotherapeutic agents were added, the combinations with pioglitazone were found with higher cytotoxicity when compared to chemotherapeutic agents alone, except for the cisplatin combination (P<0.001).

Conclusions: Indeed, Metformin, pioglitazone and DCA have anti-cancer effect on small cell lung cancer cell line which might be due to the higher amount of glucose uptake in these cells. DCA and anti-diabetic agents suppose a great advantage for a future therapeutic use in combination with antineoplastic agents in lung cancer patients.

Keywords: Small cell lung cancer; glucose uptake; metformin