CXCR4 antagonist AMD3100 reduced oxaliplatin resistance in colorectal cancer cells
10.3969/j.issn.1009-9905.2023.12.003
- VernacularTitle:CXCR4抑制剂AMD3100抑制结肠癌细胞奥沙利铂耐药的机制研究
- Author:
Gang HAN
1
;
Yu CAO
;
Yun ZHANG
;
Yan-Yan ZHANG
;
Xu ZHANG
;
Ning-Ning LIU
;
Ru JIA
;
Hang-Jun GONG
Author Information
1. 上海中医药大学附属曙光医院胃肠外科(上海 201203)
- Keywords:
Colorectal neoplasms;
Oxaliplatin;
Chemoresistance;
CXCR4;
PI3K-AKT signal pathway
- From:
Chinese Journal of Current Advances in General Surgery
2023;26(12):939-942
- CountryChina
- Language:Chinese
-
Abstract:
Objective:colorectal cancer is one of the common malignant tumors in the gas-trointestinal tract.Oxaliplatin is the first-line drug for the treatment of advanced colorectal cancer,but drug resistance often occurs.The mechanism of CXCR4 in oxaliplatin resistance of colon cancer is not clear.This study intends to explore the mechanism of CXCR4 mediated oxaliplatin resistance and the potential therapeutic value of CXCR4 inhibitor AMD3100.Methods:oxaliplatin resistant strains HCT116 were constructed.The expression of CXCR4 and the phosphorylation level of PI3K-Akt signal pathway were detected by Q-PCR and Western blot.The phosphorylation level of PI3K-Akt signal pathway was detected by Q-PCR and Western blot.The effect of AMD3100 an-tagonizing CXCR4 or combined application of Akt inhibitor LY294002 on oxaliplatin resistance of drug-resistant cells was detected by CCK8.Results:CCK-8 was used to detect the proliferation activity of Oxaliplatin in HCT116 drug resistant group compared with control cells in the absence of drugs and at different concentrations.The results showed that there was no significant change in the activity of the resistant strains,while the control cells showed a significant decrease.Q-PCR and Western blot showed that the expression of CXCR4 and the phosphorylation level of PI3K-Akt increased significantly in the drug-resistant group(P＜0.05).After administration of CXCR4 inhibitor AMD3100,CXCR4 expression and PI3K-Akt phosphorylation decreased significantly(P＜0.05).AMD3100 enhanced the sensitivity of drug-resistant cell lines to oxaliplatin.The combination of AMD3100 and Akt inhibitor LY294002 can further enhance the sensitivity of drug-resistant cell lines to oxaliplatin.Conclusion:CXCR4 mediated activation of PI3K-Akt signaling pathway plays an important role in the resistance of colon cancer to oxaliplatin.AMD3100 may become a potential therapeutic drug against chemoresistance of colon cancer.
