T4 reduces cisplatin resistance by inhibiting AEG-1 gene expression in lung cancer cells
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 wilf...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-07-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-15643-3 |
| _version_ | 1811323424898809856 |
|---|---|
| author | Tian-jiao Song Xiao-hong Lin Ping-ting Huang Yu-qing Chen Li-min Chen |
| author_facet | Tian-jiao Song Xiao-hong Lin Ping-ting Huang Yu-qing Chen Li-min Chen |
| author_sort | Tian-jiao Song |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T13:54:54Z |
| format | Article |
| id | doaj.art-dc312b772f03493da8fe05dad9bc804d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T13:54:54Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dc312b772f03493da8fe05dad9bc804d2022-12-22T02:44:14ZengNature PortfolioScientific Reports2045-23222022-07-011211710.1038/s41598-022-15643-3T4 reduces cisplatin resistance by inhibiting AEG-1 gene expression in lung cancer cellsTian-jiao Song0Xiao-hong Lin1Ping-ting Huang2Yu-qing Chen3Li-min Chen4Department of Emergency, Fujian Provincial HospitalDepartment of Respiratory Medicine, The Affiliated Hospital of Putian UniversityDepartment of Respiratory Medicine, Affiliated Union Hospital of Fujian Medical UniversityDepartment of Respiratory Medicine, Affiliated Union Hospital of Fujian Medical UniversityDepartment of Respiratory Medicine, Affiliated Union Hospital of Fujian Medical UniversityAbstract 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.https://doi.org/10.1038/s41598-022-15643-3 |
| spellingShingle | Tian-jiao Song Xiao-hong Lin Ping-ting Huang Yu-qing Chen Li-min Chen T4 reduces cisplatin resistance by inhibiting AEG-1 gene expression in lung cancer cells Scientific Reports |
| title | T4 reduces cisplatin resistance by inhibiting AEG-1 gene expression in lung cancer cells |
| title_full | T4 reduces cisplatin resistance by inhibiting AEG-1 gene expression in lung cancer cells |
| title_fullStr | T4 reduces cisplatin resistance by inhibiting AEG-1 gene expression in lung cancer cells |
| title_full_unstemmed | T4 reduces cisplatin resistance by inhibiting AEG-1 gene expression in lung cancer cells |
| title_short | T4 reduces cisplatin resistance by inhibiting AEG-1 gene expression in lung cancer cells |
| title_sort | t4 reduces cisplatin resistance by inhibiting aeg 1 gene expression in lung cancer cells |
| url | https://doi.org/10.1038/s41598-022-15643-3 |
| work_keys_str_mv | AT tianjiaosong t4reducescisplatinresistancebyinhibitingaeg1geneexpressioninlungcancercells AT xiaohonglin t4reducescisplatinresistancebyinhibitingaeg1geneexpressioninlungcancercells AT pingtinghuang t4reducescisplatinresistancebyinhibitingaeg1geneexpressioninlungcancercells AT yuqingchen t4reducescisplatinresistancebyinhibitingaeg1geneexpressioninlungcancercells AT liminchen t4reducescisplatinresistancebyinhibitingaeg1geneexpressioninlungcancercells |