Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma

Zhuang,Zhiming; Lin,Jiangui; Huang,Yiqun; Lin,Tianqi; Zheng,Zhouda; Ma,Xudong

doi:10.3892/ol.2017.6587

Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma

Authors:
- Zhiming Zhuang
- Jiangui Lin
- Yiqun Huang
- Tianqi Lin
- Zhouda Zheng
- Xudong Ma
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Affiliations: Department of Urology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363000, P.R. China, Department of Hematology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363000, P.R. China
Published online on: July 15, 2017 https://doi.org/10.3892/ol.2017.6587
Pages: 3437-3444
Copyright: © Zhuang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Notch 1 is a key component of the Notch pathway, which performs a crucial role in clear cell renal cell carcinoma (CCRCC) development. The present study aimed to investigate whether Notch 1 could serve as a potential target for CCRCC treatment. Firstly, an association analysis was performed using 52 CCRCC cases and 30 normal controls. The results indicated that Notch 1 protein expression in renal tissues was closely associated with the incidence of CCRCC. In addition, higher Notch 1 expression in CCRCC tissues was positively associated with higher tumor‑node‑metastasis stage and Fuhrman grade, in addition to larger tumor size. Subsequently, an in vitro study was conducted to examine the biological functions of Notch 1 in CCRCC 786‑O cells through inhibiting the Notch 1 expression with Notch 1‑specific small interfering RNA (siRNA). As a result, the inhibition of Notch 1 expression by increasing concentrations of Notch 1‑specific siRNA dose‑dependently decreased cell proliferation and increased cell apoptosis in 786‑O cells. Furthermore, B‑cell lymphoma‑2 and procaspase‑3 expression exhibited a dose‑dependent decrease accompanied with a dose‑dependent inactivation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway in Notch 1 siRNA‑treated 786‑O cells. These findings demonstrated that Notch 1 was associated with CCRCC carcinogenesis and progression, the underlying mechanism of which was that Notch 1 acted as an activator for cell proliferation and a suppressor for cell apoptosis through the Akt/mTOR signaling‑dependent pathway in CCRCC. In conclusion, the present study confirmed that Notch 1 is a valuable target against cell survival and proliferation in CCRCC treatment.

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