Lung cancer is the most malignant form of cancer and has the highest morbidity and mortality worldwide. Due to drug resistance, the current chemotherapy for lung cancer is not effective and has poor therapeutic effects. Tripchlorolide (T4), a natural extract from the plant Tripterygium wilfordii, has powerful immunosuppressive and antitumour effects and may become a potential therapeutic agent for lung cancer. Therefore, this study aimed to investigate the effect of T4 on reducing chemoresistance in lung cancer cells and to explore the mechanism. 1. A549 and A549/DDP cells were separately transfected with AEG-1 overexpression and AEG-1 knockdown plasmids. A549/DDP cells were divided into the A549/DDP empty group, T4 group, and T4 + AEG-1 overexpression group. A CCK-8 assay was used to evaluate the proliferation of cells in each group. RT–qPCR and Western blotting were used to detect the expression of AEG-1 and MDR-1. Expression of AEG-1 in A549 and A549/DDP cells was positively correlated with cisplatin resistance. When the AEG-1 protein was overexpressed in A549 cells, the lethal effect of cisplatin on A549 cells was attenuated (all P < 0.05). After the AEG-1 protein was knocked down in A549/DDP cells, cisplatin was applied. The lethal effect was significantly increased compared to that in the corresponding control cells (all P < 0.05). AEG-1 protein expression gradually decreased with increasing T4 concentration in A549 and A549/DDP cells. Resistance to cisplatin was reduced after the addition of T4 to A549/DDP cells (P < 0.05), and this effect was enhanced after transfection with the AEG-1 knockdown plasmid. T4 plays an important role in increasing the sensitivity of lung cancer cells to cisplatin.

BackgroundLung cancer is one of the deadliest diseases in the world. Most lung cancer patients are resistant to chemotherapy drugs. In our study, we investigated whether T4 can reduce the resistance of lung cancer cells to chemotherapeutic drugs through the action of AEG-1.Materials and Methods1.A549 and A549/DDP cells were respectively transfected with overexpressing AEG-1 and knockdown AEG-1 plasmid. A549 and A549/DDP cells were added 0、25、50、100、200nM T4 respectively. 200nM T4 was selected for following experiments. A549/DDP cells were divided into A549/DDP empty group, T4 group, T4+AEG-1 overexpressing group. CCK8 assay was used to detect the proliferation of cells in each group. RT-qPCR and Western blotting were used to detect the expression of AEG-1 and MDR-1.ResultsAs expected, the expression of AEG-1 in A549 and A549/DDP cells is positively correlated with cisplatin resistance. When AEG-1 protein was overexpressed in A549 cells, the lethal effect of cisplatin on A549 cells was attenuated (all P<0.05). After AEG-1 protein was knocked down in A549/DDP cells, cisplatin was applied to the A549/DDP cells. The lethal effect was significantly increased compared to that in the control cells (all P<0.05). The expression of AEG-1 protein gradually decreased with increasing concentration of T4 in A549 and A549/DDP cells; The resistance to cisplatin was reduced after the addition of T4 to A549/DDP cells (P<0.05), and this effect was enhanced after transfection with the AEG-1 plasmid. ConclusionIn summary, T4 is important for increasing the sensitively of lung cancer cells to cisplatin. AEG-1 may be a key protein involved in this effect and may have an important impact on the survival rate of chemotherapy in patients with lung cancer in the future.