OncoTargets and Therapy (Oct 2020)
Delicaflavone Reverses Cisplatin Resistance via Endoplasmic Reticulum Stress Signaling Pathway in Non-Small Cell Lung Cancer Cells
Abstract
Xuewen Wang,1,* Bing Chen,1– 3,* Danfen Xu,1 Zhijun Li,4 Yuxia Sui,5,6 Xinhua Lin1– 3 1Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Nano Medical Technology Research Institute, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4School of Pharmacy, Fujian Medical University, Fuzhou 350180, Fujian, People’s Republic of China; 5Department of Pharmacy, Shengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, People’s Republic of China; 6Department of Pharmacy, Fujian Provincial Hospital, Fuzhou 350001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinhua LinDepartment of Pharmaceutical Analysis, Fujian Medical University, No. 1 Xueyuan Road, University Town, Fuzhou 350122, People’s Republic of ChinaTel/Fax +86 13906909638Email [email protected] SuiDepartment of Pharmacy, Fujian Provincial Hospital, No. 134 Dong Street, Fuzhou 350001, People’s Republic of ChinaTel/Fax +86 15959090652Email [email protected]: The incidence and mortality of lung cancer continue to increase around the world; in 2018, new lung cancer cases accounted for 11.6% of all cancer cases, and lung cancer deaths accounted for 18.4% of cancer deaths. Cisplatin (DDP) is a first-line chemotherapy drug for lung cancer; however, DDP resistance can lead to a poor prognosis in patients with lung cancer. Therefore, reversing DDP resistance is a treatment goal.Materials and Methods: Cell counting kit-8 (CCK8) assays, wound healing analyses, Transwell assays, in vitro tumor xenografts, and flow cytometry were used to detect the proliferation, migration, invasion, and apoptosis of multidrug resistant A549/DDP and PC9/DDP cells, respectively. Western blot was performed to detect protein levels of cleaved caspase-3, CHOP, and GRP78.Results: Delicaflavone inhibited DDP resistance of lung cancer cells and decreased proliferation in a dose- and time-dependent manner. It also decreased migration and invasion and enhanced apoptosis. Western blots showed that delicaflavone overcame DDP resistance by increasing the expression of GRP78 and CHOP and the apoptosis-related protein cleaved caspase-3.Conclusion: Delicaflavone can reverse DDP resistance in A549/DDP and PC9/DDP cells by inhibiting cell proliferation and migration and enhancing apoptosis and cleaved caspase-3 levels by increasing the expression of CHOP and GRP78 protein via the endoplasmic reticular stress pathway. It could be a useful therapeutic adjunct to treat DDP-resistant lung cancer.Keywords: delicaflavone, Cisplatin; DDP, lung cancer, endoplasmic reticulum stress
