Suppression of GRP78 sensitizes human colorectal cancer cells to oxaliplatin by downregulation of CD24
- Jingle Xi
- Yufan Chen
- Shangbin Huang
- Fei Cui
- Xinying Wang
Affiliations: Department of Oncology, Nanfang Hospital, Guangzhou, Guangdong 510515, P.R. China, Department of Orthopaedic Surgery, Nanfang Hospital, Guangzhou, Guangdong 510515, P.R. China, Department of General Surgery, Taixin Hospital, Dongguan, Guangdong 523000, P.R. China, Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China
- Published online on: April 20, 2018 https://doi.org/10.3892/ol.2018.8549
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Glucose‑regulated protein 78 (GRP78) is an endoplasmic reticulum stress signaling regulator with anti‑apoptotic properties. It has been demonstrated to promote tumor proliferation, survival and metastasis, and to confer resistance against a large variety of therapies. CD24 is a glycosyl‑phosphatidylinositol‑anchored protein, which is known to have a role in tumor progression, particularly in colorectal cancer (CRC). In the present study, oxaliplatin (L‑OHP) was demonstrated to decrease the expression of CD24 in HT29 cells. Knockdown of CD24 using small interfering RNA resulted in sensitization of HT29 cells to L‑OHP. By contrast, overexpression of CD24 rendered SW480 cells resistant to L‑OHP, which indicated that CD24 antagonized L‑OHP‑induced cytotoxicity. A co‑immunoprecipitation assay revealed that GRP78 physically associates with CD24. L‑OHP suppresses the expression of GRP78 and CD24, in part come from the inhibition of interaction between the two. Suppression of GRP78 caused downregulation of CD24 expression and enhanced L‑OHP‑induced CD24 inhibition. Furthermore, down‑regulation of GPR78 with a pharmacological inhibitor sensitized the CRC cells to L‑OHP. Collectively, the present results indicate that CD24 antagonizes L‑OHP‑induced cytotoxicity and that GRP78 is involved in this process. A novel mechanism via which CRC cells acquire resistance to L‑OHP was thereby revealed. Use of a combination of compounds which suppress GRP78 may help to improve the effectiveness of L‑OHP in the treatment of CRC.