[Effect of bortezomib in inducing apoptosis of imatinib-resistant K562 cells and the mechanism]

Autor: Jia-Ye, Hua, Xu-Hong, Zhou, Shu-Ting, Ouyang, Yong-Bin, Wu
Rok vydání: 2017
Předmět:
Zdroj: Nan fang yi ke da xue xue bao = Journal of Southern Medical University. 37(8)
ISSN: 1673-4254
Popis: OBJECTIVE: To investigate the effect of bortezomib in inducing apoptosis in imatinib-resistant K562 (K562R) cells and its possible mechanism. METHODS: K562 cells were cultured in gradient concentrations of imatinib for several months to generate imatinib-resistant K562 cells. The viability of K562R cells treated with bortezomib was measured using CCK-8 cell proliferation assay, and the cell apoptosis was analyzed by flow cytometry with annexin V/PI dual staining. Western blotting was used to detect the protein expressions of Mcl-1, Bcl-2 and Bcr/Abl. RESULTS: K562R cell line was successfully established, which showed 31.8 folds of imatinib resistance compared with the naïve cells. Bortezomib treatment produced dose-and time-dependent inhibitory effect on the proliferation of both K562 cells and K562R cells and dose-dependently induced apoptosis in K562R cells. Combination of bortezomib with imatinib significantly enhanced the apoptosis of the cells. Western blotting showed that bortezomib treatment dose-dependently decreased the protein levels of both Mcl-1and Bcr/Abl in K562R cells without affecting bcl-2 protein expression. CONCLUSION: Bortezomib can inhibit the proliferation of K562R cells and induce cell apoptosis possibly by down-regulating Mcl-1 and Bcr/Abl expression and enhancing Mcl-1 cleavage.
Databáze: OpenAIRE