SPOCK1 silencing decreases 5-FU resistance through PRRX1 in colorectal cancer

SPOCK1 is an extracellular proteoglycan and involved in tumor growth and metastasis in various cancers. 5-fluorouracil (5-FU) is commonly used for the treatment of colorectal cancer (CRC) in patients who receive concurrent chemoradiotherapy. However, the relationship between development of resistanc...

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Published in:Pathology, research and practice research and practice, 2022-06, Vol.234, p.153895-153895, Article 153895
Main Authors: Qu, Yu-Ling, Liu, Xiao-Li, Zhao, Shan-Yu, Zhai, Xue-Feng
Format: Article
Language:English
Subjects:
5-fluorouracil
Apoptosis
Cell Line, Tumor
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Drug resistance
Drug Resistance, Neoplasm - genetics
Fluorouracil - pharmacology
Fluorouracil - therapeutic use
Gene Expression Regulation, Neoplastic - genetics
HCT116 Cells
Homeodomain Proteins - metabolism
Humans
Proteoglycans - metabolism
Proteoglycans - therapeutic use
PRRX1
SPOCK1
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Summary:SPOCK1 is an extracellular proteoglycan and involved in tumor growth and metastasis in various cancers. 5-fluorouracil (5-FU) is commonly used for the treatment of colorectal cancer (CRC) in patients who receive concurrent chemoradiotherapy. However, the relationship between development of resistance to 5-FU and SPOCK1 remain unclear. In this study, we established two 5-fluorouracil (5-FU)-resistant CRC cell lines, HCT116/FU and LOVO/FU, and found that SPOCK1 is upregulated in 5-FU-resistance CRC cells compared with its parental cell line. knockdown of SPOCK1 in 5-FU-resistant CRC cells increases their sensitivity to 5-FU. In contrast, transient transfection of SPOCK1 enhanced HCT116 and LOVO cell resistance to 5-FU and reduced cell apoptosis. Mechanistically, SPOCK1 promoted 5-FU resistance by regulating PRRX1 expression and the downstream apoptosis signaling pathway. Taken together, our results revealed for the first time that SPOCK1 plays a crucial role in the resistance of CRC cells to 5-FU and indicated that targeting SPOCK1 may be a promising therapeutic strategy to overcome 5-FU resistance in CRC.
ISSN:0344-0338
1618-0631
DOI:10.1016/j.prp.2022.153895