Comparative Effect of Tyrosine Kinase Inhibitors in Human Cancer Cell Lines
نویسندگان
چکیده
Purpose: This study compared the in vitro activity of small molecule tyrosine kinase inhibitors (TKI’s) erlotinib, dasatinib and sorafenib in human cancer cell lines of different tumor origins HCT 116 (colon carcinoma), MCF7 (breast carcinoma) and H460 (non-small cell lung carcinoma). Methods: Cytotoxicity assay was performed to determine the IC50 concentrations of TKI’s-erlotinib, dasatinib, sorafenib against HCT 116, MCF7 and H460 cell lines. Cell cycle analysis was done using Flow cytometry (FACS). Anti-proliferative effect was analyzed by colony forming assay. Western blot technique was used to investigate the effect of TKI’s on the expression of cyclin D1 protein in cancer cell lines. Results: Results indicated that erlotinib was less potent having IC50>30μM compared to dasatinib and sorafenib in all three cancer cell lines. Dasatinib was more potent than sorafenib. The data indicated dasatinib’s IC50 as 0.14 μM, 0.67 μM, 9.0 μM and sorafenib’s IC50 as 18.6 μM, 16.0 μM, 18.0 μM in HCT 116, MCF7 and H460 respectively. This study showed that sorafenib was very potent in inducing cytotoxicity in HCT 116, MCF7, H460 cells (P < 0.05, < 0.01, < 0.001), however dasatinib was found to be highly effective in MCF7 cells only (P < 0.001). Our results in clonogenic assay indicated that dasatinib and sorafenib showed decrease in colony growth in all three cell lines. Moreover, western blot analysis showed that dasatinib and sorafenib significantly decreased cyclin D1 expression in MCF7 H460cells (P < 0.001) (P < 0.05) respectively. Conclusion: We can conclude that our results are in accordance with reported findings of sorafenib and dasatinib. We established the hypothesis that sorafenib and dasatinib can be used in colon, breast and lung cancer. However sorafenib and dasatinib have the potential in the clinic, but in order to overcome the limitations of multi targeted tyrosine kinase inhibitors detailed studies can be performed using more cell lines as well as cell signalling mechanism needs to be elucidated.
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