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KMID : 0939920200520020622
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대한암학회지
2020 Volume.52 No. 2 p.622 ~ p.633
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CXCL-13 Regulates Resistance to 5-Fluorouracil in Colorectal Cancer
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Zhang Guolin
Luo Xin
Zhang Wei
Chen Engeng
Xu Jianbin
Wang Fei
Cao Gaoyang
Ju Zhenyu
Jin Dongai
Huang Xuefeng
Zhou Wei
Song Zhangfa
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Abstract
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Purpose: 5-Fluorouracil (5-Fu) is used as a conventional chemotherapy drug in chemotherapy for patients with advanced colorectal cancer, but many patients still suffer from treatment failure due 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 prognosis in patients with colorectal cancer. This study is designed to reveal the important role of 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 separately by enzyme-linked immunosorbent assay. In cell assays, cell viability is detected by Cell Counting Kit-8. Therefore, the recombinant human CXCL-13 was used to simulate its high expression in 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 culture medium exchange experiments and cytokine arrays of colorectal cancer resistant and non-resistant cells. Clinical studies showed that CXCL-13 is highly expressed in the serum of 5-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 antibody overcame 5-Fu resistance, and knockdown of CXCL-13 expression by siRNA also reduced 5-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 also provide a novel target for 5-Fu?resistant colorectal cancer in prevention and treatment strategies.
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KEYWORD
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CXCL13, 5-Fluorouracil, Colorectal neoplasms, Drug resistance, Chemokines
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