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. 2018 May 22;9(11):2046-2053.
doi: 10.7150/jca.24474. eCollection 2018.

A Study on Effect of Oxaliplatin in MicroRNA Expression in Human Colon Cancer

Jasmine Evert  1 , Surajit Pathak  2   3 , Xiao-Feng Sun  2 , Hong Zhang  1
Affiliations

A Study on Effect of Oxaliplatin in MicroRNA Expression in Human Colon Cancer

Jasmine Evert et al. J Cancer. .

Abstract

Colorectal cancer is a commonly diagnosed malignancy and also the major cause of death worldwide. Chemotherapy is the primary therapy for advanced colorectal cancer. Although oxaliplatin has potential effect in colorectal cancer therapy, the molecular mechanisms involved in its cytotoxic effects are not well elucidated. This study outlines the regulatory effects of oxaliplatin on miRNAs expression in colon cancer cells and correlates it with the changing microRNA expression with p53 and p73 expression status in cells. HCT116p53+/+ and HCT116p53-/- cells were exposed to oxaliplatin, and the cellular viability was determined by XTT. p73 was knocked down using siRNA and the tumor cells were then treated with oxaliplatin. The expression profile of 384 miRNAs was determined by TaqMan® human miRNA array and calculated by the ∆∆Ct method. Cellular viability was found to decrease after the treatment with oxaliplatin in a dose-dependent manner. The wild-type p53 cells were found to be more sensitive than the null-p53 derivatives. A selective set of miRNAs were either up-regulated or down-regulated in response to the oxaliplatin treatment with a presumable role of p53 and p73 proteins. The miRNAs expression is known to influence the pharmacodynamic mechanisms of oxaliplatin and these effects have been observed to be regulated by p53 and p73. Our results may therefore provide more evidence for identifying a suitable biomarker for the diagnosis of colon cancer.

Keywords: Oxaliplatin; colon cancer cells.; miRNAs; p53; p73.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Chemosensitivity of HCT116p53+/+ and HCT116p53-/- colon cancer cells. After allowing the cells to attach in 96-well plates for 24 hours, oxaliplatin was added with a final concentration ranging from 0 - 60 µM. After 48 hours, cellular viability was determined using the XTT assay. Three independent experiments were performed in triplicate and the data represents the mean ± SD.
Figure 2
Figure 2
Expression of TAp73 examined by Western blot, Protein expression of TAp73 after gene knockdown by siRNA and oxaliplatin treatment in colon cancer cell lines HCT116p53+/+ and HCT116p53-/-. The cells were treated with oxaliplatin (2 μM) 24 hours after transfection. 72 hours post-transfection, TAp73 expression became markedly reduced compared to non-interfering siRNA-transfected cells.
Figure 3
Figure 3
A, B, C, D Effect of oxaliplatin on the relative expression of several miRNA in colon cancer cell lines HCT116p53+/+ and HCT116p53-/-. miRNAs have the potential to act as molecular markers or even novel targets for treatment, and an increased understanding of the role of miRNAs in chemo response might aid in improving the efficacy of oxaliplatin treatment.
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