The induction of metformin inhibitory effects on tumor cell growth in hypoxic condition

It is aimed to evaluate the actual anti-cancerous effects of metformin on cancer cells in hypoxic condition. non-cancerous cells (hek293) and cancer cells (mcf-7) were cultured in both hypoxia and normoxia conditions and treated with different concentrations of metformin. the proliferation,apoptosis,and necrosis rate were assessed using mtt test and annexin v assay. the s6k1 phosphorylation was assessed using western blotting. zymography was used to measure the activity of metalloproteinase-9 (mmp-9). metformin treatment inhibited proliferation of cancer cells in the optimal concentration of 10 mm under hypoxia condition,while it showed no effects on non-cancerous cell viability. the statistical analysis of mtt assay indicated that the pro-apoptotic function of metformin for cancer cells under hypoxia condition compared to normoxia was significant with different metformin concentrations (p>0.01). however,the effect of metformin treatments for non-cancerous cells under hypoxia condition compared to normoxia was not significant. western-blot analysis indicated a significant decrease in s6k1 phosphorylation in cancer cells under hypoxia condition (p>0.05). nevertheless,there was no considerable difference between normoxia and hypoxia conditions in non-cancerous cells. mmp-9 zymography analysis revealed that the highest inhibition of mmp-9 activity was observed in hypoxia condition by 20mm of metformin concentration only in cancer cell. the results indicate that in hypoxia condition metformin exerts its anti-cancerous function by inhibiting proliferation and tumor progression and inducing cell apoptosis more effectively than normoxia condition. in line with cancer cell conditions,most importantly hypoxic condition,metformin can be considered as a potential anti-cancerous drug. © autumn 2015,iran j allergy asthma immunol. all rights reserved.