Seema2018-08-302018-08-302024-08-132018-08-302018-08-302024-08-132012Seema (2012) Effect of metform on insuln mediated proliferation of lung cancer cell lines. 2012.https://kr.cup.edu.in/handle/32116/1729Background: The incidence of cancer in diabetes mellitus (DM) patients is a matter of concern. Lung cancer is the most commonly diagnosed cancer and leading cause of death in males. Smoking is the main risk factor contributing to lung cancer progression. The occurrence of cancer is more with the type 2 DM. Besides, hyperglycemia and endogenous insulinaemia exist together for a long duration as a result of insulin resistance. As a consequence of this, the mitogenic activity of insulin is amplified. Moreover, other growth factors, and hormones are activated under the influence of insulin that further enhances this effect. It is also related to obesity, central fat accumulation, physical inactivity and smoking. The nicotine of smoke induces oxidative stress and endothelial malfunction creating metabolic abnormalities in lung cancer. In this perspective, role of insulin sensitizing drug, metformin in inhibiting the growth proliferation of lung cancer cells is hereby explored. Objective: The present study was aimed to evaluate the growth proliferation effect of insulin on non small cell lung carcinoma cell lines. It also proposed to evaluate role of metformin in preventing 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 a range of concentrations from 1nM to 10'M. This was followed by the metformin (concentrations from 1'M to 50mM) treatment for 24 hours along with insulin (500'M for A549 and 1mM for H1299). The proliferations were assessed by MTT dye reduction test and the percentage of the survival of the treated cells was compared with the control. One way ANOVA was used for the data analysis and the proliferation between cell lines were evaluated by student's t-test and two way analysis of variance (Two way ANOV). Results: Both the cell lines exhibited a significant proliferation (p<0.001) with the concentrations of insulin. Insulin stimulated the proliferation approximately by two fold and 1.78 times for A549 cells and H1299 cell line respectively compared to control cells. The growth of two lung carcinoma cell lines were significantly (p<0.001) inhibited by metformin treatment for 24 hours. The maximum reduction in growth was 73% and 67% for A549 and H1299 respectively for a concentration of 50mM of metformin compared to the control. The results followed a dose dependant response pattern for insulin as well as metformin treatment. Concentration at which 50% inhibition of growth observed (IC50) was comparable for both the cell lines. Conclusions: Insulin in high circulating concentrations can augment the growth proliferation of lung cancer cells. Metformin can inhibit this insulin mediated proliferation of lung cancer cells in a multifaceted way. The mechanism of action is independent of p53 and liver kinase B1.en-USNon small cell lung carcinomaDiabetes mellitusInsulin resistanceMetforminInsulinMphil DissertationT00015