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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