Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

MiR-494-3p mediates oxaliplatin resistance of colorectal cancer cells via PTEN/AKT pathway

Yongming Yu¹, Zhou Wu², Zhonglei Shen², Yangyang Xie², Yisheng Cao², Jiangfan Zhu³

¹Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200100, China; ²Department of Colorectal Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315000, Zhejiang Province, China; ³Bariatric and Metabolic Surgery, Shanghai Tenth Hospital, Tongji University School of Medicine, Shanghai 200100, China.

For correspondence:- Jiangfan Zhu Email: zhujiangfan@hotmail.com

Accepted: 28 March 2022 Published: 30 April 2022

Citation: Yu Y, Wu Z, Shen Z, Xie Y, Cao Y, Zhu J. MiR-494-3p mediates oxaliplatin resistance of colorectal cancer cells via PTEN/AKT pathway. Trop J Pharm Res 2022; 21(4):727-732 doi: 10.4314/tjpr.v21i4.7

© 2022 The authors.
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Abstract

Purpose: To unravel the influence of miR-494-3p on the insensitivity of colorectal cancer (CRC) cells to oxaliplatin.

Methods: The mRNA level of miR-494-3p in oxaliplatin-resistant HT-29 cells was evaluated with reverse transcript-polymerase chain reaction (RT-PCR). The cells were treated with miR-494-3p suppressor or mimic, and then apoptotic changes were determined flow cytometrically. Resistance-related gene expressions were measured using RT-PCR and western blotting. In addition, in vivo mouse experiments were conducted.

Results: MiR-494-3p expression in oxaliplatin-resistant HT-29 cells was much higher than that in parental HT-29 cells, accompanied by increased levels of MRP, P-gp, and AKT phosphorylation (p-AKT), and decreased phosphatase and tensin homolog (PTEN) (p < 0.001). The miR-494-3p mimic suppressed oxaliplatin-induced parental HT-29 cell apoptosis, while miR-494-3p inhibitor promoted oxaliplatin-resistant HT-29 cell apoptosis and decreased the levels of p-AKT, MRP and P-gp, while upregulating PTEN (p < 0.001). Furthermore, AKT inhibitor had similar effects as miR-494-3p inhibitor (p < 0.001). Experiments using nude mice demonstrated that inhibition of miR-494-3p accentuated the sensitivity of oxaliplatin-resistant HT-29 cells to oxaliplatin (p < 0.05).

Conclusion: Suppression of miR-494-3p attenuates oxaliplatin insensitivity to CRC cells via a mechanism which may involve PTEN/AKT pathway. Therefore, miR-494-3p may be an effective target for overcoming drug resistance of CRC.

Keywords: MiR-494-3p, Oxaliplatin, Colorectal cancer, Cell apoptosis