Figure 6

Metformin-induced cisplatin resistance is reversed by glutathione depletion in OSCC cells. The glutathione synthesis inhibitor, BSO was used to confirm the involvement of elevated glutathione levels in metformin induced cisplatin resistance in OSCC cells. MTT assays for cytotoxicity were performed as described, with cells treated with cisplatin alone (C), or in the presence 0.4 mM BSO (CB), or metformin and cisplatin (CM), or metformin and cisplatin in the presence of 0.4 mM BSO (CMB). Data is expressed as the percentage difference of LD₅₀ values for each treatment relative to cisplatin alone (n = 3, mean ± SD). Predictably, the inhibition of glutathione synthesis increased cisplatin toxicity as LD₅₀ values for cisplatin-BSO treated cells were significantly lower than cisplatin alone. Importantly, the presence of the inhibitor ablates the protective effect of metformin, with LD₅₀ values for cisplatin-metfomin-BSO treated cells approaching those of cisplatin alone.