Ailanthone Increases Cisplatin-induced Apoptosis and Autophagy in Cisplatin Resistance Non-small Cell Lung Cancer Cells through the PI3K/AKT/mTOR Pathway.

INTRODUCTION

The effectiveness of therapy is strongly impacted by the resistance of lung cancer cells to cisplatin. The objective of this research is to characterize the impact of ailanthone on cisplatin resistance in non-small cell lung cancer (NSCLC) and examine any potential in vivo and in vitro molecular pathways.

METHODS

Following treatment of A549/DDP cells with ailanthone and cisplatin, cell survival and apoptosis were measured using flow cytometry and Cell Counting Kit-8 (CCK- 8) assays, respectively. mRFP-GFP-LC3 adenovirus transfection was used to track autophagy, and protein expression levels were analyzed by western blotting. Hematoxylin and eosin (H&E) staining was used after the organs of the mice were removed for in vivo investigations. In A549/DDP cells, ailanthone and cisplatin together induced autophagy and apoptosis in a dose and time-dependent manner (P< 0.05). After receiving combined treatment with ailanthone and cisplatin, the expression levels of cleaved caspase- 3, Bcl-2, cleaved PARP, Beclin1L, and C3B-II were considerably elevated by inhibiting the PI3K/AKT/mTOR signaling pathway.

RESULT

Our findings show that ailanthone, without causing adverse effects in vivo, greatly suppressed the growth of A549/DDP-grafted tumors and improved the anti-tumor efficaciousness of cisplatin.

CONCLUSION

According to this study, ailanthone may increase sensitivity to cisplatin and promote autophagy and death in NSCLC A549/DDP cells through the signaling pathway of PI3K/AKT/mTOR.