Growth inhibition of arsenic trioxide in bcr-abl mutant cells and the potential mechanism / 白血病·淋巴瘤

ABSTRACT

Objective To investigate the effect of arsenic trioxide (ATO) on the growth inhibition of bcr-abl mutant cell lines in vitro and to explore its potential mechanism. Methods The growth inhibition of ATO on bcr-abl wild type cell lines (K562, KBM5 and 32Dp210) and imatinib(IM)-resistant cell lines (K562R, KBM5R, 32Dp210T315I, 32Dp210Q252H, 32Dp210Y253H, 32Dp210M351T and 32Dp210E255K) were measured by trypan blue exclusion. Apoptosis was assayed by AnnexinV and PI staining. Glutathione (CSH) levels were detected by DTNB colorimetry of Glutathione Assay Kit. Results ATO inhibited cell growth in both bcr-abl wild type and IM-resistant mutant type cells in a dose dependent manner. ATO significantly inhibited growth of bcr-abl point mutant cells compared with the corresponding wild type cells, and the IC50 of ATO in mutant cells was lower than that in wild type, while the IC50 in no point mutant cells K562R was not different compared with that in wild type cells K562. The GSH levels in bcr-abl point mutant cells were lower than that in the corresponding wild type cells(P =0.00106-0.0358) , but that in K562 was quite similar with K562R cells(P = 0.315). After depletion of intracellular GSH by using BSO, the growth inhibition of ATO in both bcr-abl point mutant cells and wild type cells was significantly enhanced. Conclusion The growth inhibition of ATO on bcr-abl point mutant cells is remarkably more effective than that on wild type cells, which may be related with intracellular GSH. ATO would be a potential therapeutic select against CML with bcr-abl point mutation including the T315I mutation.