[Bcl-2 inhibitor ABT-737 enhances the cisplatin-induced apoptosis in breast cancer T47D cells].

OBJECTIVE

To study the effect of ABT-737 combined with cisplatin on apoptosis of breast cancer cell line T47D cells.

METHODS

T47D cells cultured in vitro was used for this experiment. Cell proliferation was measured by MTT assay. The expression of apoptosis-related protein was determined by Western blot. Morphological changes of apoptotic cells were observed by fluorescence microscopy. The apoptosis rate was examined by flow cytometry.

RESULTS

The MTT assay showed that ABT-737 significantly decreased the IC(50) of cisplatin in T47D cells [(26.00 ± 1.41) µmol/L of single cisplatin vs. (13.00 ± 1.11) µmol/L of combination (ABT-737 + cisplatin)]. As a single agent, ABT-737 did not inhibit the proliferation of T47D cells, but enhanced the inhibitory effect of cisplatin in a dose-dependent manner. The detection of the cleavage of PARP showed that ABT-737 lowered the doses of cisplatin to induce apoptosis and shortened the induction time of apoptosis in T47D cells. Compared with the single use of cisplatin, the combination of ABT-737 and cisplatin accelerated the cleavage of PARP and caspase3, but did not alter the expression levels of Bcl-2, Bcl-X(L), and Bax. Both flow cytometry and fluorescence microscopy showed that ABT-737 combined with cisplatin significantly increased the apoptosis induction in T47D cells (2.3% ± 0.1 % in the control, 30.0% ± 0.8% in the cisplatin alone, and 49.0% ± 0.5% in the cisplatin + ABT-737 groups, P < 0.05).

CONCLUSION

The Bcl-2 inhibitor ABT-737 can significantly enhance cisplatin-induced apoptosis in human breast cancer T47D cells in vitro.