Tian, Yu and Li, Peiwei and Xiao, Zhaohua and Zhou, Jie and Xue, Xia and Jiang, Ning and Peng, Chuanliang and Wu, Licun and Tian, Hui and Popper, Helmut and Poh, Mau-Ern and Marcucci, Fabrizio and Zhang, Chengke and Zhao, Xiaogang (2021) Triptolide inhibits epithelial-mesenchymal transition phenotype through the p70S6k/GSK3/beta-catenin signaling pathway in taxol-resistant human lung adenocarcinoma. Translational Lung Cancer Research, 10 (2). 1007+. ISSN 2218-6751, DOI https://doi.org/10.21037/tlcr-21-145.
Full text not available from this repository.Abstract
Chemotherapy is one of the primary treatments for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), however, chemoresistance develops over time and is a bottleneck to effective chemotherapy worldwide. Therefore, the development of new potent therapeutic agents to overcome chemoresistance is of utmost importance. Triptolide is a natural component extracted from Tripterygium Wilfordii, a Chinese plant; our study aimed to evaluate its anti-tumor effects in taxol-resistant human lung adenocarcinoma and investigate its molecular mechanisms of chemoresistance. Methods: Triptolide's inhibition of cell viability was detected by sulforhodamine B (SRB) assay. Cell cycle was measured by flow cytometry and cell apoptosis was assessed by flow cytometry and western blot. Expression of 0-catenin was analyzed by western blot and immunofluorescence (IF). The anti-tumor effects of triptolide were determined using a subcutaneous in-vivo model. Cell proliferation and apoptosis were evaluated by immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. The expression level of p-p70S6K and p-GSK-3 alpha/0 was evaluated by western blot and IHC. Results: Triptolide inhibited cell proliferation, induced S-phase cell cycle arrest and apoptosis in taxolresistant A549 (A549/TaxR) cells. Moreover, intraperitoneal injection of triptolide resulted in a significant delay of tumor growth without obvious systemic toxicity in mice. Additionally, triptolide reversed epithelialmesenchymal transition (EMT) through repression of the p70S6K/GSK3/0-catenin signaling pathway. Conclusions: Our study provides evidence that triptolide can reverse EMT in taxol-resistant lung adenocarcinoma cells and impairs tumor growth by inhibiting the p70S6K/GSK3/0-catenin pathway, indicating that triptolide has potential to be used as a new therapeutic agent for taxol-resistant lung adenocarcinoma.
| Item Type: | Article |
|---|---|
| Funders: | National Natural Science Foundation of China (NSFC)[81874396], Major Program of Shandong Province Natural Science Foundation[ZR2018ZC0232], Jinan Clinical Medicine Research Program for Thoracic Cancer[201912007], Special Construction Project Fund for Taishan Mountain Scholars of Shandong Province |
| Uncontrolled Keywords: | Lung adenocarcinoma;Triptolide;Chemoresistance;Epithelial-mesenchymal transition (EMT);Wnt |
| Subjects: | R Medicine R Medicine > RC Internal medicine R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 15 Sep 2022 03:11 |
| Last Modified: | 15 Sep 2022 03:11 |
| URI: | http://eprints.um.edu.my/id/eprint/34573 |
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