Effect of the Nrf2‑ARE signaling pathway on biological characteristics and sensitivity to sunitinib in renal cell carcinoma

Ji,Shiliang; Xiong,Yufeng; Zhao,Xingxing; Liu,Yanli; Yu,Li  Qiang

doi:10.3892/ol.2019.10156

Effect of the Nrf2‑ARE signaling pathway on biological characteristics and sensitivity to sunitinib in renal cell carcinoma

Authors:
- Shiliang Ji
- Yufeng Xiong
- Xingxing Zhao
- Yanli Liu
- Li Qiang Yu
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Affiliations: Department of Pharmacy, Suzhou Science and Technology Town Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215153, P.R. China, Department of Clinical Laboratory, Guangdong Women and Children Health Hospital, Guangzhou, Guangdong 510000, P.R. China, Department of Neonatology, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China, College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu 215123, P.R. China, Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
Published online on: March 18, 2019 https://doi.org/10.3892/ol.2019.10156
Pages: 5175-5186

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Abstract

The aim of the present study was to examine the effects of the nuclear factor erythroid‑2 related factor 2‑antioxidant‑responsive element (Nrf2‑ARE) signaling pathway on the biological characteristics and sensitivity to targeted therapy in human renal cell carcinoma (RCC) cells. RCC tissues and adjacent tissues were collected and assessed by immunohistochemistry to determine the expression of Nrf2, NAD(P)H dehydrogenase [quinone] 1 (NQO1) and heme oxygenase‑1 (HO‑1) to analyze the clinicopathological features of RCC. A series of in vitro experiments were conducted to analyze the biological characteristics of Nrf2‑ARE signaling in RCC. The renal cancer cell line, 786‑0 was used, and cells was divided into a mock group, negative control group and small hairpin (sh)RNA‑Nrf2 group. A Cell Counting Kit‑8 assay was performed alongside flow cytometry to detect cell viability, cell cycle stage and apoptosis following treatment with sunitinib. The results demonstrated that Nrf2, NQO1 and HO‑1 were significantly upregulated in RCC tissues compared with adjacent tissues and were associated with tumor node metastasis stage, Fuhrman classification and lymph node metastasis. Following shRNA‑Nrf2 transfection, the 786‑0 cells demonstrated a significant decrease in viability, cell invasion and scratch healing rate, and the mRNA and protein expression levels of Nrf2, NQO1, HO‑1 and glutathione transferase were significantly decreased, which enhanced the sensitivity to sunitinib, arrested cells in the G0/G1 phase and increased apoptosis. In conclusion, Nrf2‑ARE signaling is important for RCC progression, and its inhibition may increase sensitivity to targeted drugs to provide novel developments for RCC treatment.

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