BKM120 inhibits malignant rhabdoid tumor of the kidney through induction of apoptosis and G0/G1 phase arrest

作者全名："Liu, Jiayan; Mi, Tao; Zhang, Zhaoxia; Jin, Liming; Li, Maoxian; Zhanghuang, Chenghao; Li, Mujie; Wang, Jinkui; Wu, Xin; Wang, Zhaoying; Tan, Xiaojun; Wang, Zhang; He, Dawei"

作者地址："[Liu, Jiayan; Mi, Tao; Zhang, Zhaoxia; Jin, Liming; Li, Maoxian; Zhanghuang, Chenghao; Li, Mujie; Wang, Jinkui; Wu, Xin; Wang, Zhaoying; Tan, Xiaojun; Wang, Zhang; He, Dawei] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Dept Urol,Minist Educ,Key Lab Child Dev & Disorder, Chongqing 400014, Peoples R China; [Liu, Jiayan; Mi, Tao; Zhang, Zhaoxia; Jin, Liming; Li, Maoxian; Zhanghuang, Chenghao; Li, Mujie; Wang, Jinkui; Wu, Xin; Wang, Zhaoying; Tan, Xiaojun; Wang, Zhang; He, Dawei] Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing 400014, Peoples R China; [He, Dawei] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China"

通信作者："He, DW (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China."

来源：EUROPEAN JOURNAL OF PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001001785200001

JCR分区：Q1

影响因子：4.2

年份：2023

卷号：951

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：MRTK; BKM120; PI3K; Akt; Apoptosis; Cell phase arrest

摘要："Malignant rhabdoid tumor of the kidney (MRTK) has an inferior prognosis and is insensitive to radiotherapy and chemotherapy. Search for novel, potent medicinal agents is urgent. Herein, data on the gene expression and clinical characteristics of malignant rhabdoid tumors (MRT) were retrieved from the TARGET database. Prognosis-related genes were identified by differential analysis and one-way cox regression analysis, and prognosis-related signalling pathways were identified by enrichment analysis. The prognosis-related genes were imported into the Connectivity Map database for query, and BKM120 was predicted and screened as a potential therapeutic agent for MRTK. A combination of high-throughput RNA sequencing and Western blot verified that the PI3K/Akt signaling pathway is associated with MRTK prognosis and is overactivated in MRTK. Our results outlined that BKM120 inhibited the proliferation, migration, and invasion ability of G401 cells and induced apoptosis and cell cycle G0/G1 phase arrest. In vivo, BKM120 inhibited tumor growth and had no significant toxic side effects. Western blot and immunofluorescence results confirmed that BKM120 could reduce the expression of PI3K and p-AKT, critical proteins of the PI3K/Akt signaling pathway. BKM120 inhibits MRTK by inhibiting PI3K/Akt signalling pathway to induce apoptosis and cell cycle G0/G1 phase arrest, which is antici-pated to give the clinical treatment of MRTK a new direction."

基金机构：　

基金资助正文：