Reverting doxorubicin resistance in colon cancer by targeting a key signaling protein, steroid receptor coactivator

Xiong,Sang; Xiao,Gong‑Wei

doi:10.3892/etm.2018.5912

Reverting doxorubicin resistance in colon cancer by targeting a key signaling protein, steroid receptor coactivator

Authors:
- Sang Xiong
- Gong‑Wei Xiao
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Affiliations: Department of Oncology, Xuhui District Central Hospital, Shanghai 200031, P.R. China
Published online on: February 28, 2018 https://doi.org/10.3892/etm.2018.5912
Pages: 3751-3758
Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although there have been notable improvements in treatments against cancer, further research is required. In colon cancer, nearly all patients eventually experience drug resistance and stop responding to the approved drugs, making treatment difficult. Steroid receptor coactivator (SRC) is an oncogenic nuclear receptor coactivator that serves an important role in drug resistance. The present study generated a doxorubicin‑resistant colon cancer cell line, in which the upregulation/activation of SRC was responsible for drug resistance, which in turn activated AKT. Overexpression of receptor tyrosine kinase‑like epidermal growth factor receptor and insulin‑like growth factor 1 receptor also induced SRC expression. It was observed that doxorubicin resistance in colon cancer also induced epithelial to mesenchymal transition, a decrease in expression of epithelial marker E‑cadherin and an increase in the expression of mesenchymal markers, including N‑cadherin and vimentin. Additionally, the present study indicated that SRC acts as a common signaling node, and inhibiting SRC in combination with doxorubicin treatment in doxorubicin‑resistant cells aids in reversing the resistance. Thus, the present study suggests that activation of SRC is responsible for doxorubicin resistance in colon cancer. However, further research is required to understand the complete mechanism of how drug resistance occurs and how it may be tackled to treat patients.

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