Inhibition of γ‑secretase induces G2/M arrest and triggers apoptosis in renal cell carcinoma

Wu,Kerong; Zhang,Li; Lin,Yiwei; Yang,Kai; Cheng,Yue

doi:10.3892/ol.2014.2078

Inhibition of γ‑secretase induces G2/M arrest and triggers apoptosis in renal cell carcinoma

Authors:
- Kerong Wu
- Li Zhang
- Yiwei Lin
- Kai Yang
- Yue Cheng
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Affiliations: Department of Urology, Ningbo First Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, P.R. China, Department of Urology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200000, P.R. China, Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: April 22, 2014 https://doi.org/10.3892/ol.2014.2078
Pages: 55-61

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Abstract

The present study was performed to explore the effects of Notch pathway inhibition on the proliferation and apoptosis of renal carcinoma cells. The expression levels of Notch1 and Jagged1 were examined by western blot analysis and immunohistochemistry in pathologically identified clear cell renal cell carcinoma (RCC) and normal kidney tissues. Next, γ‑secretase inhibitor was used to suppress the Notch pathway in renal carcinoma cell lines. The proliferation was detected by 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay and flow cytometry analysis was performed to determine the apoptosis, as well as cell cycle alteration. The expression of Notch1 and Jagged1 proteins was detected to be higher in tumor tissues than in non‑neoplastic tissues by western blot analysis. The positive staining rates of Notch1 and Jagged1 in clear cell RCC were higher than in normal kidney tissues [95.3 vs. 36.4% (P<0. 05); 93.0 vs. 42.4% (P<0.05), respectively]. The expression levels of Notch1 and Jagged1 were found to statistically correlate with tumor size, grade, TNM stage and disease relapse. The suppression of the Notch pathway was associated with cell proliferation inhibition, as well as induced G2/M phase cell cycle arrest and cell apoptosis. The Notch pathway may be important in oncogenesis of clear cell RCC and the γ‑secretase inhibitor may be a potential agent for target therapy of RCC.

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