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Journal of Cancer
2021;12 (7): 1952-1959.

Cyr61 mediates oxaliplatin resistance in colorectal cancer cells by regulating Bcl-xL expression.

Yanfang Song, Yanli Kang, Zhen Lin, Menglu Zeng, Pengchong Shi, Jia Lin, Pingxia Lu, Li Luo, Yingping Cao, Xianjin Zhu
Author Information
  1. Yanfang Song: Department of Clinical Laboratory, Affiliated People Hospital of Fujian University of Traditional Chinese Medicine, 602 Bayiqi Road, Fuzhou, Fujian 350001, China.
  2. Yanli Kang: Department of Clinical Laboratory, Fujian Provincial Hospital, 134 Dongjie Road, Fuzhou, Fujian 350001, China.
  3. Zhen Lin: Department of Clinical Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian 350001, China.
  4. Menglu Zeng: Department of Clinical Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian 350001, China.
  5. Pengchong Shi: Department of Clinical Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian 350001, China.
  6. Jia Lin: Department of Clinical Laboratory, Affiliated People Hospital of Fujian University of Traditional Chinese Medicine, 602 Bayiqi Road, Fuzhou, Fujian 350001, China.
  7. Pingxia Lu: Department of Clinical Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian 350001, China.
  8. Li Luo: Department of Clinical Laboratory, Affiliated People Hospital of Fujian University of Traditional Chinese Medicine, 602 Bayiqi Road, Fuzhou, Fujian 350001, China.
  9. Yingping Cao: Department of Clinical Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian 350001, China.
  10. Xianjin Zhu: Department of Clinical Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian 350001, China.
PMID: 33753993 DOI: 10.7150/jca.48891

Abstract

Although the clinical application of oxaliplatin (L-OHP) has improved the survival of colorectal cancer (CRC) patients, approximately half of patients with CRC fail to achieve good clinical outcomes, indicating resistance to L-OHP therapy. Cysteine-rich protein 61 (Cyr61), a multifunctional extracellular matrix protein, is highly expressed in a variety of tumors; increased Cyr61 expression is known to be closely involved in the chemotherapeutic resistance of many tumors, but its role in the L-OHP resistance of CRC cells has not been studied. In this study, we aimed to investigate the role of Cyr61 in the L-OHP resistance of CRC cells and examine the underlying mechanism. Our findings showed that the mRNA and protein levels of Cyr61 in L-OHP-resistant cells were significantly increased compared with those in nonresistant cells. Knockdown of Cyr61 enhanced the chemosensitivity of L-OHP-resistant cells to L-OHP. Mechanistically, we found that overexpression of Cyr61 decreased L-OHP-induced apoptosis in drug-resistant CRC cells through the regulation of Bcl-xL. Collectively, our results revealed for the first time that Cyr61 plays a crucial role in the resistance of CRC cells to L-OHP and indicated that targeting Cyr61 may be a promising therapeutic strategy to overcome L-OHP resistance in CRC.

Keywords

colorectal cancer cysteine-rich protein 61 oxaliplatin resistance

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