Different expression of FoxO3/Keap1/Nrf2 pathway in tumor cells and drug resistant tumor cells

Abstract

Abstract:

AIM: To detect the different expression of FoxO3/Keap1/Nrf2 pathway in normal and drug resistant tumor cells so as to investigate the effect of FoxO3/Keap1/Nrf2 signal on drug resistance of tumor cell. METHODS: Cell lines of A549 (resistant to cisplatin) and HCT-8 (resistant to 5-FU) were constructed and verified by the MTT assay. The mRNA and protein expressions of FoxO3/Keap1/Nrf2 pathway members in drug-resistant tumor cells and non- drug-resistant tumor cells were evaluated by QRT-PCR and Western blot. RESULTS:The drug resistance of A549/DDP was significantly stronger than A549 cell (P<0.05), the resistance index was 5.25 times; the drug resistance of HCT-8/5-FU was significantly stronger than HCT-8 cell (P<0.05), the resistance index was 31.67 times; the mRNA expressions of FoxO3, Keap1 and Akt in A549/DDP and HCT-8/5-FU cells were decreased compared with normal control cells, while mRNA expression levels of Nqo1 and Nrf2 were increased; the protein expression of FoxO3 and Keap1 in A549 DDP and HCT-8/5-FU cells were decreased compared with normal control cells, while protein expression levels of p-Akt, Nqo1 and Nrf2 were increased. CONCLUSION: FoxO3/Keap1/Nrf2 signaling pathway is related with tumor resistance, which was referential for further study of this pathway and for exploring therapeutic strategies to reduce drug resistance of cancer.

Key words: FoxO3/Keap1/Nrf2 signaling pathway, A549, HCT-8, drug resistance

CLC Number:

R965.2

YE Haizhu, CHEN Yajuan, ZHAO Wenying, LIU Xiaoping. Different expression of FoxO3/Keap1/Nrf2 pathway in tumor cells and drug resistant tumor cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(8): 859-865.

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