Effects of poly(ADP-ribose)polymerase inhibitor AG014699 combined with chemotherapy on the proliferation of triple-negative breast cancer cell line MDA-MB-231 / 中国医学科学院学报

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effects of poly(ADP-ribose)polymerase (PARP) inhibitor AG014699 alone and combined with docetaxel (DTX) or carboplatin (CBP) on the proliferation of triple-negative breast cancer cell line MDA-MB-231 and to investigate whether PARP inhibitor AG014699 combined with chemotherapy could play a synergistic antitumor effect.</p><p><b>METHODS</b>MDA-MB-231 cells were treated by PARP inhibitor AG014699 alone or combination with DTX or CBP. Cell proliferation was measured by cell counting kit-8 assay. The combined effect was evaluated by q value less than 0.85, in the range of 0.85 and 1.15, more than 1.15, which respectively meant that the combined effect of the drugs was antagonistic, additive, and synergistic.</p><p><b>RESULTS</b>Treatment with PARP inhibitor AG014699, DTX, or CBP alone inhibited the proliferation, induced apoptosis and blocked the cell cycle. The cell viability of AG014699 (10 µmol/L) combined with DTX (10(-8), 10(-7), 10(-6), 10(-5) mol/L) or CBP (10(-5), 10(-4) mol/L) were lower than that of the drug used alone, and q value was between 0.85 and 1.15, suggesting the combined effect was additive. The cell viability of AG014699 (10 µmol/L) combined with CBP (10(-3) mol/L) was lower than that of the drug used alone, and q value was more than 1.15, suggesting the combined effect was synergetic. A combination of PARP inhibitor AG014699 and DTX or CBP promoted apoptosis and increased the proportion of G2/M stage cells.</p><p><b>CONCLUSION</b>PARP inhibitor AG014699 combined with DTX or CBP can remarkably inhibit MDA-MB-231 cell proliferation, showing additive or synergistic antitumor effects.</p>