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敲低EBP1通过激活p38/HIF-1α途径促进阿霉素诱导的肾透明细胞癌细胞凋亡。

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

作者信息

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

机构信息

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.

出版信息

Oncol Lett. 2025 Feb 6;29(4):172. doi: 10.3892/ol.2025.14918. eCollection 2025 Apr.

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

摘要

肾透明细胞癌(KIRC)是一种常见的泌尿系统癌症。尽管KIRC的治疗有了显著改善,但中晚期患者仍无法获得合适的药物。阿霉素被广泛用作治疗多种癌症的化疗药物。然而,其使用会带来有害的副作用和耐药性。ErbB3结合蛋白()在KIRC中高表达,敲低可降低p38丝裂原活化蛋白激酶(p38MAPK)的磷酸化水平和HIF-1α的表达。因此,本研究旨在评估联合使用阿霉素和敲低在KIRC细胞系中的有效性。实验使用了KIRC细胞系786-O和769-P,并采用短发夹RNA技术特异性敲低基因的表达。处理后,通过蛋白质免疫印迹法分析细胞,以检测p38MAPK磷酸化水平和HIF-1α表达的变化。结果表明,敲低通过p38MAPK/HIF-1α途径显著增强了阿霉素对KIRC细胞的抗肿瘤作用。总之,敲低联合阿霉素可能是治疗KIRC的一种潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2c3/11834144/7a688817de9a/ol-29-04-14918-g00.jpg

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