Knockdown of EBP1 promotes doxorubicin-induced apoptosis in renal clear cell carcinoma cells through activation of the p38/HIF-1&alpha; pathway

Ma,Lina; Huo,Jiaqi; Cao,Shuxia; Yue,Yuyang; Li,Xiangdan; Tian,Shengri; Liu,Lan

doi:10.3892/ol.2025.14918

Knockdown of EBP1 promotes doxorubicin-induced apoptosis in renal clear cell carcinoma cells through activation of the p38/HIF-1α pathway

Authors:
- Lina Ma
- Jiaqi Huo
- Shuxia Cao
- Yuyang Yue
- Xiangdan Li
- Shengri Tian
- Lan Liu
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Affiliations: Key Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji, Jilin 133000, P.R. China, Department of Pathology, Yanbian University Hospital, Yanji, Jilin 133000, P.R. China, Department of Urology, Yanbian University Hospital, Yanji, Jilin 133000, P.R. China
Published online on: February 6, 2025 https://doi.org/10.3892/ol.2025.14918
Article Number: 172
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Kidney clear cell carcinoma (KIRC) is a prevalent urological cancer. Despite substantial improvements in KIRC care, patients with intermediate and advanced stages of the disease lack access to appropriate medications. Doxorubicin is widely used as a chemotherapy drug for the treatment of multiple types of cancer. However, its use is associated with harmful side effects and drug resistance. ErbB3-binding protein (EBP1) is highly expressed in KIRC, and the knockdown of EBP1 reduces the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and the expression of HIF-1α. Therefore, the present study aimed to evaluate the effectiveness of combined doxorubicin administration and EBP1 knockdown in KIRC cell lines. The KIRC cell lines 786-O and 769-P were used for the experiments, and short hairpin RNA technology was employed to specifically knock down the expression of the EBP1 gene. After treatment, cells were analyzed by western blotting to detect changes in p38MAPK phosphorylation levels and HIF-1α expression. The results showed that EBP1 knockdown significantly enhanced the antitumor effect of doxorubicin on KIRC cells through the p38MAPK/HIF-1α pathway. In conclusion, the knockdown of EBP1 in combination with doxorubicin may be a potential strategy for the treatment of KIRC.

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