Polyphyllin II (PPII) Enhances the Sensitivity of Multidrug-resistant A549/DDP Cells to Cisplatin by Modulating Mitochondrial Energy Metabolism

多叶酸 II (PPII) 通过调节线粒体能量代谢增强多药耐药 A549/DDP 细胞对顺铂的敏感性

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作者:Lian Peng, Renyi Yang, Zhibing Wang, Huiying Jian, Xiaoning Tan, Jian Li, Zuomei He, Rui Huang, Puhua Zeng, Wenhui Gao

Aim

Cisplatin resistance often leads to treatment futility and elevated mortality rates in patients with lung cancer. One promising strategy to address this challenge involves the integration of traditional Chinese medicine (TCM) with chemotherapeutic drugs. Currently, the potential synergistic effect and underlying mechanism of polyphyllin II (PPII) and cisplatin combination in combating cisplatin (DDP) resistance in lung cancer remain unexplored. Materials and

Conclusion

The combination of PPII and cisplatin effectively modulated the mitochondrial function, thereby reversing drug resistance in A549/DDP cells. This innovative combination therapy shows significant promise as a novel strategy for overcoming cisplatin resistance in lung cancer.

Methods

In this study, we established a cisplatin resistance model using A549 cells and explored the underlying mechanisms of PPII in combination with cisplatin in A549/DDP resistant cells. Specifically, we assessed the impact of PPII combined with cisplatin on A549/DDP cell proliferation, viability, and the expression of apoptosis-related proteins. To gain deeper insights into the underlying mechanism, we examined the effects of PPII and cisplatin on mitochondrial function in A549/DDP cells.

Results

This combination induced cell cycle arrest at both the S phase and G2/M phase in A549/DDP cells, thereby promoting apoptosis. Western blotting confirmed that DDP acted synergistically with PPII to enhance the expression of apoptotic proteins, diminish the expression of anti-apoptotic proteins, and promote the expression of anti-proliferation proteins in the mitochondrial pathway of A549/DDP cells.

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