Nghiên cứu In Vitro xác định sự đáp ứng ở mức độ phân tử của dòng tế bào ung thư đại trực tràng HT-29 đối với thuốc Selumetinib

Abstract

Objectives: 1) To evaluate the changes of Selumetinib-resistant CR HT-29/SR cells to Selumetinib, compared with the original HT-29/P cells and 2) To determine molecular characterization in selumetinib-resistant CR HT-29/SR cells compared with the original HT-29/P cells. Methods: Generation of resistant cells, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), cologenic formation and Western blot assays were used to determine the ability of Selumetinib response at the molecular level of the Selumetinib-resistant HT-29/SR cells compared to the original HT-29 cells. Results: Compared to the original HT-29/P cells, the higher proliferation rate of the Selumetinib-resistant HT-29/SR cells, demonstrated by the results of MTS and cologenic formation assay. Furthermore, the signaling levels MAPK at Y202/T204 and AKT1/2 at S473 in the Selumetinib-resistant HT-29/SR cells were higher, compared to those in the original HT-29/P cells. In particular, the expression levels of E-Cadherin, Vimentin, and Caveolin-1 in the Selumetinib-resistant HT-29/SR cells and the original HT-29/P cells were significantly different. Compared to the original HT-29/P cells, the expression levels of Vimentin and Caveolin-1 were higher and the expression levels of E-Cadherin were lower in the Selumetinib-resistant HT-29/SR cells. Conclusion: Initial determination of the molecular response of the Selumetinib-resistant HT-29/SR cells compared to the original HT-29/P cells through the signaling pathway of MAPK and AKT and the expression levels of Caveolin-1 biomarker. Key words: Selumetinib; Colorectal cancer; HT-29 cells; Drug response; Drug resistance; In vitro.