MiRNA153 Reduces Effects of Chemotherapeutic Agents or Small Molecular Kinase Inhibitor in HCC Cells

Title:MiRNA153 Reduces Effects of Chemotherapeutic Agents or Small Molecular Kinase Inhibitor in HCC Cells

Volume: 15 Issue: 3

Author(s): Yan Chen, Fan Feng, Xudong Gao, Chunping Wang, Huiwei Sun, Cuihong Zhang, Zhen Zeng, Yinying Lu, Linjing An, Jianhui Qu, Fusheng Wang and Yongping Yang

Affiliation:

Keywords: Etoposide, HCC cells, miR-153, PTEN, paclitaxel, sorafenib.

Abstract: MicroRNA-153 (miR-153) is considered to be a tumor regulator. Silencing of miR-153 expression induced apoptosis in breast cancer cells. Data on mechanism suggest that up-regulation of miR- 153 level promotes cell proliferation via the down regulation of the expression of PTEN or FOXO1, which attenuates the proliferation of cancerous cells. This study aims to identify the effect of miR-153 on the activity of chemotherapeutic and targeted agents in HCC cells and to investigate the mechanisms involved. MTT, soft agar, trans-well and flow cytometry assays were performed to examine whether miR-153 down-regulated the activity of the chemotherapeutic and targeted drugs, Sorafenib, Etoposide and Paclitaxel in HCC cells. The rate of proliferation inhibition, relative survival rates and IC₅₀ values of each drug were calculated. Western blot and luciferase assays were performed to assess whether miR-153 modulates the expression of important genes related to cell proliferation, apoptosis or survival. Results showed that miR-153 attenuated the effect of Etoposide, Paclitaxel and Sorafenib on HepG2 cells; the IC₅₀ value increased from 0.25±0.01μmol/L to 1.02±0.14μmol/L, 0.05±0.01μmol/L to 0.14±0.02μmol/L and from 1.09±0.15μmol/L to 5.18±0.99μmol/L, respectively. In addition, miR-153 also reduced the effect of these drugs on MHCC- 97H, MHCC-97 L and L-02 cells; and it also reduced the effects of Sorafenib, Etoposide and Paclitaxel on anchorindependent growth of HepG2 cells. Over-expression of miR-153 down-regulated the activity of Etoposide and Paclitaxel on cell cycle arrest of HepG2 cells and the effect of Sorafenib on the invasion and migration of HepG2 cells. Furthermore, overexpression of miR-153 also enhanced the growth of HepG2, MHCC-97H, MHCC-97 L and L-02 cells. Mechanisms data showed that overexpression of miR-153 down regulated the activity of luciferase reporters, p15-Luc and p21-Luc; and enhanced the protein level of pro-survival or anti-apoptosis proteins Survivin and BCL-2. These results show that overexpression of miR-153 protects HepG2 cells against the effects of these drugs via multiple mechanisms, and miR-153 may be a novel target for HCC in future diagnostic and therapeutic interventions.

Cite this article as:

Chen Yan, Feng Fan, Gao Xudong, Wang Chunping, Sun Huiwei, Zhang Cuihong, Zeng Zhen, Lu Yinying, An Linjing, Qu Jianhui, Wang Fusheng and Yang Yongping, MiRNA153 Reduces Effects of Chemotherapeutic Agents or Small Molecular Kinase Inhibitor in HCC Cells, Current Cancer Drug Targets 2015; 15 (3) . https://dx.doi.org/10.2174/1568009615666150225122635