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

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 (<i>EBP1</i>) is highly expressed in KIRC, and the knockdown of <i>EBP1</i> 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 <i>EBP1</i> 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 <i>EBP1</i> gene. After treatment, cells were analyzed by western blotting to detect changes in p38MAPK phosphorylation levels and HIF-1α expression. The results showed that <i>EBP1</i> knockdown significantly enhanced the antitumor effect of doxorubicin on KIRC cells through the p38MAPK/HIF-1α pathway. In conclusion, the knockdown of <i>EBP1</i> in combination with doxorubicin may be a potential strategy for the treatment of KIRC.