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

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.