Abstract |
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.
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Authors | Lin Cao, Weipeng Hong, Peiheng Cai, Chuncao Xu, Xupeng Bai, Zhongxiang Zhao, Min Huang, Jing Jin |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 890
Pg. 173647
(Jan 05 2021)
ISSN: 1879-0712 [Electronic] Netherlands |
PMID | 33049304
(Publication Type: Journal Article)
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Copyright | Copyright © 2020. Published by Elsevier B.V. |
Chemical References |
- Antineoplastic Agents
- NF-E2-Related Factor 2
- NFE2L2 protein, human
- Phenanthrenes
- cryptotanshinone
- Transketolase
- Gefitinib
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Apoptosis
(drug effects)
- Carcinoma, Non-Small-Cell Lung
(drug therapy, metabolism)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Drug Resistance, Neoplasm
(drug effects)
- Female
- Fibroblasts
(drug effects, metabolism)
- Gefitinib
(pharmacology, therapeutic use)
- Gene Knockdown Techniques
- Humans
- Lung Neoplasms
(drug therapy, metabolism, pathology)
- Male
- Mice, Inbred BALB C
- Mice, Nude
- NF-E2-Related Factor 2
(metabolism)
- Phenanthrenes
(pharmacology, therapeutic use)
- Transketolase
(antagonists & inhibitors, biosynthesis, genetics)
- Up-Regulation
(drug effects)
- Xenograft Model Antitumor Assays
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