Cryptotanshinone strengthens the effect of gefitinib against non-small cell lung cancer through inhibiting transketolase
Autor: | Cai Peiheng, Weipeng Hong, Min Huang, Zhongxiang Zhao, Jing Jin, Chuncao Xu, Lin Cao, Xupeng Bai |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Lung Neoplasms NF-E2-Related Factor 2 medicine.medical_treatment Mice Nude Antineoplastic Agents Apoptosis Transketolase 03 medical and health sciences 0302 clinical medicine Gefitinib In vivo Carcinoma Non-Small-Cell Lung Cell Line Tumor Medicine Animals Humans Lung cancer neoplasms Cell Proliferation Pharmacology Gene knockdown Mice Inbred BALB C business.industry Cell growth Fibroblasts Phenanthrenes medicine.disease Xenograft Model Antitumor Assays In vitro respiratory tract diseases Up-Regulation 030104 developmental biology Drug Resistance Neoplasm Gene Knockdown Techniques Cancer research Female business Adjuvant 030217 neurology & neurosurgery medicine.drug |
Zdroj: | European journal of pharmacology. 890 |
ISSN: | 1879-0712 |
Popis: | Lung cancer is the leading cause of cancer-related mortality and causes more than a million deaths per year. Gefitinib is the first-line agent of advanced lung cancer, however, resistance to gefitinib becomes a major problem in clinical application. Transketolase (TKT) is a key enzyme functioning between the oxidative arm and the non-oxidative arm of the pentose phosphate pathway. In this study, we firstly found that the expression of TKT was remarkably up-regulated in NSCLC cells, while the knockdown of TKT could inhibit cell proliferation and enhance the effect of gefitinib on NSCLC cells, which indicated the role of TKT in treating advanced lung cancer. Cryptotanshinone (CTS) is a natural active compound possessing anti-cancer effect. Here we demonstrated that CTS could strengthen the effect of gefitinib on NSCLC cells via inhibition of TKT in vitro and in vivo. Moreover, Nrf2 was involved in the repression of CTS on TKT expression. Collectively, these findings indicated the role of TKT in lung cancer progression and may provide novel therapeutic strategies to overcome resistance to gefitinib. Furthermore, CTS may serve as a new candidate in adjuvant treatment of advanced lung cancer. |
Databáze: | OpenAIRE |
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