Research Paper Volume 13, Issue 18 pp 21914—21940

Metformin-induced chemosensitization to cisplatin depends on P53 status and is inhibited by Jarid1b overexpression in non-small cell lung cancer cells

Metformin does not chemosensitize H1299 and H358 (P53 null) cells to cisplatin. The P53 null H1299 and H358 NSCLC cells (A) were not chemosensitized by combined treatment between cisplatin and metformin as it did not elevate DNA fragmentation (B), caspase 3 and 7 activation (C) or reduce cell viability as measured by MTT (D), when compared to either treatments alone. Metformin decreased the number of colonies and no colonies was observed after cisplatin treatment in H1299 and H358 cells (pE). Combined treatment also did not decrease H1299 tumor growth (F) and weight in NOD/SCID mice (G). Data represent the mean of three independent experiments. Non-significance (n.s.). H1299 cells were treated with 2mM of metformin for 72 h and 12.5μM of cisplatin (with or without metformin) for another 72 h. H358 cells were treated with 20mM of metformin for 72 h and 20μM of cisplatin (with or without metformin) for another 72 h.

Figure 5. Metformin does not chemosensitize H1299 and H358 (P53 null) cells to cisplatin. The P53 null H1299 and H358 NSCLC cells (A) were not chemosensitized by combined treatment between cisplatin and metformin as it did not elevate DNA fragmentation (B), caspase 3 and 7 activation (C) or reduce cell viability as measured by MTT (D), when compared to either treatments alone. Metformin decreased the number of colonies and no colonies was observed after cisplatin treatment in H1299 and H358 cells (p<0.05 and p<0.001, respectively) (E). Combined treatment also did not decrease H1299 tumor growth (F) and weight in NOD/SCID mice (G). Data represent the mean of three independent experiments. Non-significance (n.s.). H1299 cells were treated with 2mM of metformin for 72 h and 12.5μM of cisplatin (with or without metformin) for another 72 h. H358 cells were treated with 20mM of metformin for 72 h and 20μM of cisplatin (with or without metformin) for another 72 h.