Abstract

Background: Lung cancer and diabetes mellitus (DM) are diseases of high occurrence worldwide. Increased incidence of lung cancer in DM patients is frequently observed. In this context, an insulin-sensitizing drug, metformin (biguanides) may have inhibitory effects on the proliferation of lung cancer cells. Aim: The present study was aimed to evaluate the growth proliferation effect of insulin on nonsmall cell lung carcinoma (NSCLC) cell lines. It also proposed to assess the preventive role of metformin in insulin-mediated proliferation in p53 and liver kinase B1 (LKB1) mutant and wild-type cell lines. Materials and methods: Two non small cell lung carcinoma cell lines, A549 and H1299 (p53 and LKB1 wild-type and mutant) were used to analyze the mitogenic role of insulin by incubating for 24 hours with human recombinant insulin at concentrations of 1nM to 10μM and followed by the addition of metformin (concentrations from 1μM to 50mM) for 24 hours along with insulin (500nM for A549 and 1μM for H1299). The proliferation was assessed by MTT dye reduction test. Results: Both the cell lines exhibited a significant and dosedependent growth proliferation (p < 0.001) with different concentrations of insulin. This was effectively (p < 0.001) inhibited by metformin treatment for 24 hours. The maximum reduction in growth was 73% and 67% for A549 and H1299 respectively. Conclusions: Insulin in high circulating concentrations can augment the growth proliferation of lung cancer cells. Metformin can inhibit this in a multifaceted way, wherein the mechanism of action is independent of p53 and liver kinase B1. Clinical significance: Metformin could inhibit the insulinmediated proliferation of cells, and hence it may be considered for the new therapeutic policies for treatment of human NSCLC.

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