Lovastatin but not metformin can enhance the cytotoxic effects of gefitinib in LKB1 deficient tumour cells.

<p><i>(A and B)</i> MTT cell viability assays to evaluate the potential of metformin (0–20 mM) or lovastatin (0–100 µM) treatments to enhance the cytotoxicity of gefitinib (1–25 µM) in various LKB1 deficient cell lines including A549 (NSCLC) and HeLa and LKB1 expressing SCC25 and SCC9 cell lines. Metformin and lovastatin treatments were for 72 hrs (24 hr pretreatment) while the addition of gefitinib was for 48 hrs. <i>(C and D)</i> The Chou-Talalay method was used to distinguish between antagonistic, additive and synergistic cytotoxicity in the A549 and SCC9 with the combination of agents at various fractions of cell cytotoxicity (Fractional Effect). The Combination Index (CI) values of 1 are additive, less than 1 are synergistic and more than 1 are antagonistic and determined by CalcuSyn 2.0 software analysis. In the LKB1 deficient A549 cell line, metformin in combination with 10 µM gefitinib displayed antagonism in combination, while lovastatin in combination with 10 µM gefitinib consistently displayed synergism while in the SCC9 cell lines similar combinations of metformin or lovastatin with 10 µM gefitinib both displayed synergy in combination.