PD-0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance.

BACKGROUND

Acquired resistance of chemotherapy, especially cisplatin, is a major challenge in lung cancer treatment. We conducted this study to examine whether a cyclin D kinase 4/6 (CDK4/6) inhibitor, PD 0332991, could reverse cisplatin resistance in human lung cancer cells. In addition, we explored the underlying mechanisms.

METHOD

We used CCK-8 assay to got the IC50 of PD-0332991 and cisplatin in A549 and A549/CDDP respectively. CCK-8 assay, CalcuSyn 2.0 software, cell cycle distribution and apoptosis used to identify PD-0332991 could reverse the acquired resistance of cisplatin. At last, western-blot used to show the mechanism of PD-0332991 enhances the effects of cisplatin.

RESULTS

We found that PD-0332991 potentiated cisplatin-induced growth inhibition in both cisplatin-sensitive (A549) and cisplatin-resistant (A549/CDDP) cells via downregulation of the proliferation, induction of apoptosis (A549 increased to 7.06%; A549/CDDP increased to 7.03%), and G0/G1 cell cycle arrest (A549 increased to 9.15%; A549/CDDP increased to 49.92%). Western blot analysis revealed that PD-0332991 enhance the effect of cisplatin through inhibit Rb-E2Fs pathway.

CONCLUSIONS

These findings suggest that PD-0332991 could reverse the acquired resistance of cisplatin in lung cancer cells and provide a novel treatment strategy for lung cancer patients with cisplatin resistance.