Suppression of chloride voltage‑gated channel 3 expression increases sensitivity of human glioma U251 cells to cisplatin through lysosomal dysfunction

Zhang,Yihe; Zhou,Lei; Zhang,Juanjuan; Zhang,Lichao; Yan,Xiaoyu; Su,Jing

doi:10.3892/ol.2018.8736

Suppression of chloride voltage‑gated channel 3 expression increases sensitivity of human glioma U251 cells to cisplatin through lysosomal dysfunction

Authors:
- Yihe Zhang
- Lei Zhou
- Juanjuan Zhang
- Lichao Zhang
- Xiaoyu Yan
- Jing Su
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Affiliations: Department of Pathophysiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Pathology, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China
Published online on: May 18, 2018 https://doi.org/10.3892/ol.2018.8736
Pages: 835-842
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The mechanism of cisplatin resistance is complex. Previous studies have indicated that chloride voltage‑gated channel 3 (CLCN3) is associated with drug resistance; however, the mechanisms are not fully understood. Therefore, the present study explored the involvement of CLCN3 in cisplatin resistance in human glioma U251 cells. The effects of combined cisplatin treatment and CLCN3 suppression on cultured U251 cells were investigated. The decreased viability of cisplatin‑treated U251 cells indicated the cytotoxic effects of CLCN3 silencing. Expression of the apoptosis‑related gene TP53 and caspase 3 activation were enhanced in cisplatin‑treated U251 cells. Furthermore, the ratio of BCL2/BAX expression was decreased. Notably, CLCN3 suppression promoted cisplatin‑induced cell damage in U251 cells. Thus, the combined use of cisplatin and CLCN3 antisense had additive effects in U251 cells. In addition, the present results indicated that CLCN3 suppression decreased lysosome stabilization in U251 cells treated with cisplatin. To conclude, the present results indicated that CLCN3 suppression can sensitize glioma cells to cisplatin through lysosomal dysfunction.

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