The involvement of Aurora-A and p53 in oxaliplatin-resistant colon cancer cells

Mei-Chih Chen; Bing-Ze Yang; Wei-Wen Kuo; Shih-Hsin Wu; Tso-Fu Wang; Yu-Lan Yeh; Ming-Cheng Chen; Chih-Yang Huang

doi:10.1002/jcb.30394

The involvement of Aurora-A and p53 in oxaliplatin-resistant colon cancer cells

J Cell Biochem. 2023 Apr;124(4):619-632. doi: 10.1002/jcb.30394. Epub 2023 Mar 28.

Authors

Mei-Chih Chen^{1

2}, Bing-Ze Yang³, Wei-Wen Kuo⁴, Shih-Hsin Wu³, Tso-Fu Wang⁵, Yu-Lan Yeh⁶, Ming-Cheng Chen^{7

8}, Chih-Yang Huang^{3

9

10

11

12}

Affiliations

¹ Department of Medical Research, Translational Cell Therapy Center, China Medical University Hospital, Taichung, Taiwan.
² Department of nursing, Asia University, Taichung, Taiwan.
³ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
⁴ Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
⁵ Department of Hematology and Oncology, Hualien, Taiwan.
⁶ Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
⁷ Division of Colorectal Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
⁸ College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁹ Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
¹⁰ Department of Science, Holistic Education Center, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan.
¹¹ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
¹² Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan.

PMID: 36976911
DOI: 10.1002/jcb.30394

Abstract

Resistance to chemotherapy is the deadlock in cancer treatment. In this study, we used wild-type LOVO (LOVO^WT ), a human colon cancer cell line, and the oxaliplatin-resistant sub-clone LOVO^OR cells to investigate the molecular mechanisms of the development of drug resistance in colon cancer. Compared with LOVO^WT cells, LOVO^OR cells had a high proliferation capacity and a high percentage on the G2/M phase. The expression and activation of Aurora-A, a critical kinase in G2/M phase, were higher in LOVO^OR cells than in LOVO^WT cells. The results from immunofluorescence indicated an irregular distribution of Aurora-A in LOVO^OR cells. To evaluate the importance of Aurora-A in oxaliplatin-resistant property of LOVO^OR cells, overexpression of Aurora-A in LOVO^WT cells and otherwise knockdown of Aurora-A in LOVO^OR cells were performed and followed by administration of oxaliplatin. The results indicated that Aurora-A might contribute to the resistance of LOVO^OR cells to oxaliplatin treatment by depressing p53 signaling. The specific findings in this study provide a possibility that targeting Aurora-A might be a solution for patients who have failed oxaliplatin treatment.

Keywords: Aurora-A; colon cancer; drug resistance; oxaliplatin; p53.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Cell Line, Tumor
Colonic Neoplasms* / drug therapy
Colonic Neoplasms* / genetics
Colonic Neoplasms* / metabolism
Drug Resistance, Neoplasm
Humans
Oxaliplatin / pharmacology
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism

Substances

Oxaliplatin
Antineoplastic Agents
Tumor Suppressor Protein p53