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

• Main Authors: Minghui Liu, Liyuan Cui, Xin Li, Chunqiu Xia, Yongwen Li, Rui Wang, Fan Ren, Hongyu Liu, Jun Chen
• Format: Article
• Language: English
• Published: Wiley 2021-03-01
• Series: Thoracic Cancer
• Subjects: chemotherapy; cisplatin; drug resistance; lung cancer; PD‐0332991
• Online Access: https://doi.org/10.1111/1759-7714.13866
• ISSN: 1759-7706; 1759-7714

Abstract 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.