CXCL-13 Regulates Resistance to 5-Fluorouracil in Colorectal Cancer
- Author:
Guolin ZHANG
1
;
Xin LUO
;
Wei ZHANG
;
Engeng CHEN
;
Jianbin XU
;
Fei WANG
;
Gaoyang CAO
;
Zhenyu JU
;
Dongai JIN
;
Xuefeng HUANG
;
Wei ZHOU
;
Zhangfa SONG
Author Information
- Publication Type:Original Article
- From:Cancer Research and Treatment 2020;52(2):622-633
- CountryRepublic of Korea
- Language:0
-
Abstract:
Purpose:5-Fluorouracil (5-Fu) is used as a conventional chemotherapy drug in chemotherapy forpatients with advanced colorectal cancer, but many patients still suffer from treatment failuredue to 5-Fu resistance. Emerging observations revealed the important role of chemokine(C-X-C motif) ligand 13 (CXCL-13) in tumor microenvironment and its relationship with prognosisin patients with colorectal cancer. This study is designed to reveal the important roleof CXCL-13 in causing colorectal cancer resistance to 5-Fu.
Materials and Methods:CXCL-13 levels of patient's serum or cell culture supernatants were measured separatelyby enzyme-linked immunosorbent assay. In cell assays, cell viability is detected by Cell CountingKit-8. Therefore, the recombinant human CXCL-13 was used to simulate its high expressionin cells while its antibody and siRNA were used to reduce CXCL-13 expression in cells.
Results:In this study, we demonstrated that CXCL-13 is associated with 5-Fu resistance by culturemedium exchange experiments and cytokine arrays of colorectal cancer resistant and nonresistantcells. Clinical studies showed that CXCL-13 is highly expressed in the serum of5-Fu–resistant patients. High levels of serum CXCL-13 also predict a worse clinical outcome.The addition of recombinant CXCL-13 cytokine resulted in 5-Fu resistance, while its antibodyovercame 5-Fu resistance, and knockdown of CXCL-13 expression by siRNA also reduced5-Fu resistance, which can be saved by added recombination CXCL-13.
Conclusion:These results not only identify a CXCL-13 mediated 5-Fu resistance mechanism but alsoprovide a novel target for 5-Fu–resistant colorectal cancer in prevention and treatmentstrategies.
