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

被引:1
作者
Chen, Mei-Chih [1 ,2 ]
Yang, Bing-Ze [3 ]
Kuo, Wei-Wen [4 ]
Wu, Shih-Hsin [3 ]
Wang, Tso-Fu [5 ]
Yeh, Yu-Lan [6 ]
Chen, Ming-Cheng [7 ,8 ]
Huang, Chih-Yang [3 ,9 ,10 ,11 ,12 ,13 ]
机构
[1] China Med Univ Hosp, Translat Cell Therapy Ctr, Dept Med Res, Taichung, Taiwan
[2] Asia Univ, Dept Nursing, Taichung, Taiwan
[3] China Med Univ, Grad Inst Biomed Sci, Taichung, Taiwan
[4] China Med Univ, Dept Biol Sci & Technol, Taichung, Taiwan
[5] Dept Hematol & Oncol, Hualien, Taiwan
[6] Changhua Christian Hosp, Dept Pathol, Changhua, Taiwan
[7] Taichung Vet Gen Hosp, Dept Surg, Div Colorectal Surg, Taichung, Taiwan
[8] Natl Yang Ming Chiao Tung Univ, Coll Med, Taipei, Taiwan
[9] Hualien Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Cardiovasc & Mitochondrial Related Dis Res Ctr, Hualien, Taiwan
[10] Tzu Chi Univ Sci & Technol, Buddhist Tzu Chi Med Fdn, Holist Educ Ctr, Dept Sci, Hualien, Taiwan
[11] China Med Univ Hosp, China Med Univ, Dept Med Res, Taichung, Taiwan
[12] Asia Univ, Dept Med Lab Sci & Biotechnol, Taichung, Taiwan
[13] Hualien Tzu Chi Hosp, Cardiovasc & Mitochondria Related Dis Res Ctr, Hualien 970, Taiwan
关键词
Aurora-A; colon cancer; drug resistance; oxaliplatin; p53; OVARIAN-CANCER; BREAST-CANCER; KINASE; OVEREXPRESSION; PHOSPHORYLATION; CHECKPOINT; CHEMORESISTANCE; AMPLIFICATION; COMBINATION; LEUCOVORIN;
D O I
10.1002/jcb.30394
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Resistance to chemotherapy is the deadlock in cancer treatment. In this study, we used wild-type LOVO (LOVOWT), a human colon cancer cell line, and the oxaliplatin-resistant sub-clone LOVOOR cells to investigate the molecular mechanisms of the development of drug resistance in colon cancer. Compared with LOVOWT cells, LOVOOR 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 LOVOOR cells than in LOVOWT cells. The results from immunofluorescence indicated an irregular distribution of Aurora-A in LOVOOR cells. To evaluate the importance of Aurora-A in oxaliplatin-resistant property of LOVOOR cells, overexpression of Aurora-A in LOVOWT cells and otherwise knockdown of Aurora-A in LOVOOR cells were performed and followed by administration of oxaliplatin. The results indicated that Aurora-A might contribute to the resistance of LOVOOR 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.
引用
收藏
页码:619 / 632
页数:14
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