Enhancing effect of chidamide on the sensibility of human chronic myeloid leukemia K562/ADM cells to daunorubicin

WANG Shi-guang SI Xu-yan LI Xiao-ting LI Deng-yun WANG Li-jun WANG Peng*

doi:10.16098/j.issn.0529-1356.2019.06.009

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Acta Anatomica Sinica ›› 2019, Vol. 50 ›› Issue (6) : 754-760. DOI: 10.16098/j.issn.0529-1356.2019.06.009

Cancer Biology

Enhancing effect of chidamide on the sensibility of human chronic myeloid leukemia K562/ADM cells to daunorubicin

WANG Shi-guang¹ SI Xu-yan² LI Xiao-ting¹ LI Deng-yun¹ WANG Li-jun¹ WANG Peng^3*

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Abstract

Objective To investigate whether chidamide (CDM) could influence the sensibility of human chronic myeloid leukemia K562/ADM cells to daunorubicin (DNR) and its possible mechanism. Methods The K562 and K562/ADM cells were cultured in vitro and treated with CDM and(or) DNR for 48 hous, and then the cell viability was measured by cell counting kit-8(CCK-8) assay. The proliferation, cell cycle and apoptosis were analyzed by flow cytometry. Western blotting was performed to measure the protein levels of histon 2AX(H2AX), γH2AX (Ser139), ataxia telangiectasia mutated gene (ATM), p-ATM (Ser1981), breast cancer susceptibility protein 1(BRCA1), and p-BRCA1 (Ser1524). Results DNR remarkably inhibited the cell activity of K562/ADM cells in dose-dependent manner with a half maximal inhibitory concentration(IC50) value of 11.76 μmol/L, and the resistant factor was 18.09. Co-treatment with CMD and DNR produced a synergistic effect confidence interval(Cl)(CI<1) with a reversal fold of 8.11. DNR remarkably inhibited proliferation (P<0.05), induced G2/M phase arrest and apoptosis (P<0.05), these effects were enhanced under non-toxic concentration of CMD (P<0.05). K562/ADM cells had a significantly higher protein levels of ATM and BRCA1 than K562 cells (P<0.05). DNR significantly up-regulated the protein levels of γH2AX, p-ATM and p-BRCA1 (P<0.05), and the protein level of γH2AX appeared higher in the combination group compared to DNR alone (P<0.05); however, the co-treatment with CMD and DNR induced a decreased expression of p-ATM and pBRCA1 than the DNR alone (P<0.05). Conclusion CDM may enhance the sensibility of K562/ADM cells to DNR by up-regulating the protein level of γH2AX, and down-regulating the protein levels of p-ATM and p-BRCA1.

Key words

Chidamide / Daunorubicin / K562/ADM cell / Breast cancer susceptibility protein 1 / Histon2AX / Flow cytomertry / Human

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WANG Shi-guang SI Xu-yan LI Xiao-ting LI Deng-yun WANG Li-jun WANG Peng. Enhancing effect of chidamide on the sensibility of human chronic myeloid leukemia K562/ADM cells to daunorubicin[J]. Acta Anatomica Sinica. 2019, 50(6): 754-760 https://doi.org/10.16098/j.issn.0529-1356.2019.06.009

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