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. 2022 Jul 6;12(1):11462.
doi: 10.1038/s41598-022-15643-3.

T4 reduces cisplatin resistance by inhibiting AEG-1 gene expression in lung cancer cells

Affiliations

T4 reduces cisplatin resistance by inhibiting AEG-1 gene expression in lung cancer cells

Tian-Jiao Song et al. Sci Rep. .

Abstract

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
The expression of AEG-1 and MDR-1 in A549 and A549/DDP cells. (A) The expression of AEG-1 in mRNA level. (B) The expression of MDR-1 in mRNA level. (C) The expression of AEG-1 and MDR-1 in protein level. (DF) Quantitative analysis of AEG-1 and MDR-1 protein expression.
Figure 2
Figure 2
The effect of AEG-1 and MDR-1 on the killing effect of platinum in A549 and A549/DDP cells. (AD) A549 and A549/DDP cells overexpress AEG-1 and knock down AEG-1, AEG-1 and MDR-1 respectively; (E,F) Quantitative analysis of WB results; (G,H) overexpress AEG-1 and knock down AEG-1 respectively. The killing effect of platinum on A549 and A549/DDP cells.
Figure 3
Figure 3
The effect of T4 on regulating AEG-1 expression. (A,B) The mRNA expression of AEG-1 and MDR-1 in T4, A549 and A549/DDP cells. (C,D) The protein expression of AEG-1 and MDR-1 in T4, A549 and A549/DDP cells. (E,F) Quantitative analysis of AEG-1 and MDR-1 protein expression.
Figure 4
Figure 4
The effect of T4 on the killing effect of cisplatin. (AC) AEG-1 and MDR-1 protein expression in A549/DDP cells; (D) The killing effect of cisplatin on A549/DDP cells.

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