Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

Yan,Zejun; Jiang,Junhui; Li,Fan; Yang,Weiming; Xie,Guohai; Zhou,Cheng; Xia,Shujie; Cheng,Yue

doi:10.3892/or.2015.3807

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

Authors:
- Zejun Yan
- Junhui Jiang
- Fan Li
- Weiming Yang
- Guohai Xie
- Cheng Zhou
- Shujie Xia
- Yue Cheng
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Affiliations: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, P.R. China, Department of Urology, Ningbo First Hospital, Medical College of Ningbo University, Ningbo, Zhejiang 315010, P.R. China, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: February 16, 2015 https://doi.org/10.3892/or.2015.3807
Pages: 1791-1798

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Abstract

Cisplatin (cis-diaminodichloroplatinum, CDDP) is one of the most effective chemotherapeutic agents that has been widely used in the treatment of many malignancies, including muscle invasive bladder cancer. However, development of CDDP resistance in cancer cells is a major obstacle to the effective treatment of bladder cancer. Therefore, the development of chemosensitizers to overcome the acquired resistance to chemotherapeutic agents is crucial. Previous studies have confirmed that the epidermal growth factor receptor (EGFR) and its signaling pathways are important in the chemoresistance of cancer cells against CDDP‑induced cell apoptosis. In a preliminary study we showed that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is the natural ligand of EGFR, and that the extracellular leucine-rich repeat (LRR) domain and immunoglobulin-like domains of LRIG1 were able to bind to the extracellular domain of EGFR, resulting in the downregulation of EGFR expression. Based on these findings, we hypothesized that LRIG1 may enhance the chemosensitivity of bladder cancer cells to CDDP. In the present study, LRIG1 was overexpressed by the adenovirus vector to determine the effect of LRIG1 on chemosensitivity in the T24 bladder cancer cell line and explored the possible mechanisms. The results showed that CDDP inhibited the growth of the T24 cell line and induced activation of EGFR. Overexpression of LRIG1 increased the inhibitory effect of CDDP on the T24 cell line, which may be associated with inactivation of the EGFR signaling pathway, followed by the decrease of Bcl-2 expression and a concomitantly induced expression of Bax. Based on these results, we concluded that the upregulation of LRIG1 expression inhibited the EGFR signaling pathway, activated the mitochondrial pathway of apoptosis and eventually increased the sensitivity of bladder cancer cells to CDDP.

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