Ginkgol C17:1 Reversed The Drug Resistance Of Cisplatin Through The Nrf2/Keap1 Signaling Pathway Regulated By Autophagy In The Lung Cancer

Lung cancer is the most malignant tumor in our country,and non-small cell lung cancer(NSCLC)accounts for 80-85% of all lung cancers.It is necessary to cure lung cancer patients with chemotherapy treatment,but platinum-based combination chemotherapy cells are prone to drug resistance,which is the main reason for the cancer chemotherapy treatments fail.Currently.Studies have confirmed that Ginkgol C17:1 has the highest anti-tumor activity among ginkgo monomers,but it is not clear whether Ginkgol C17:1 can be used as an adjuvant drug of cisplatin to enhance the sensitivity of chemotherapy.The purpose of this study was to elucidate the effect of Ginkgol C17:1 and cisplatin on the proliferation,migration,invasion and other biological activities of lung cancer cells at the cell level in vitro.And under the action of Ginkgol C17:1,studing the mechanism of drug resistance of lung cancer cells in autophagy and Nrf2 / Keap1 signal pathway,and then discuss wherther Ginkgol C17:1 and cisplatin combination can reverse the drug resistance of lung cancer cells to cisplatin resistant.Methods: lung cancer drug-resistant cell line A549/DDP was taken as the research object,and the effects of Ginkgol C17:1 on the proliferation,migration and invasion of lung cancer cells were studied in vitro by using the MTT assay and Transwell assay.The effect of Ginkgol C17:1 on drug-resistant lung cancer stem cells was detected by flow cytometry.Using Wertern Blotting and autophagy double standard adenovirus method,investigating the mechanism of Ginkgol C17:1 on drug resistance of lung cancer resistant cells.Experimental contents and results of this study:(1)The function of Ginkgol C17:1 and cisplatin on the proliferationon in the lung cancer cells.(2)Combination of Ginkgol C17:1 and cisplatin restrained the migration and invasion of lung cancer cell A549/DDP.(3)Combination of Ginkgol C17:1 and cisplatin inhibited Nrf2/Keap1 signaling pathway and the expression of drug-resistant proteins.(4)Combination of Ginkgol C17:1 and cisplatin suppressed the production of autophagy and expression of autophagy protein,(5)Autophagy inhibitor enhanced ginkgol C17:1 with cisplatin in the suppression of autophagy flux and the proteins of autophagy,Nrf2/Keap1 signaling pathway and drug resistance.(6)Autophagy activator reversed the inhibitory effects of ginkgol C17:1 and cisplatin combination on autophagy flux and the proteins of autophagy,Nrf2/Keap1 signaling pathway and drug resistance.