Fig. 5: AMPK activator synergizes the antiproliferative activity of EGFR TKI in vitro and in vivo.
From: Cigarette smoke-induced LKB1/AMPK pathway deficiency reduces EGFR TKI sensitivity in NSCLC
a, b The cell counting assay of H292 (a) and A549 pcDNA and LKB1 WT (b) treated with erlotinib, metformin or their combination for the indicated days. c–e CSE- and B[α]P-selected stable H292 cells treated with erlotinib and metformin were subjected to MTT assays (c). The combination index of CSE- and B[α]P-treated H292 cells in response to erlotinib plus metformin (d) or gefitinib plus metformin (e) was determined by using CompuSyn. f–i H292 cells were inoculated subcutaneously into NOD-SCID mice followed by treatment with erlotinib, metformin, or the combination for the indicated days. The tumor size (f, g) and weight (h) were measured. Phosphorylation of ACC and 4EBP1, and expression of Ki67 in these tissue sections were quantified from IHC staining results (i). n = 7 mice for each group. j Overall survival curve of the metformin and non-metformin cohort of patients with NSCLC and T2DM who received TKI treatment. Data are shown as mean ± SEM from experiments performed in triplicate. *P < 0.05; **P < 0.01; ***P < 0.001.
