2. Academic Validation
  3. BKM120 inhibits malignant rhabdoid tumor of the kidney through induction of apoptosis and G0/G1 phase arrest

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

  • Eur J Pharmacol. 2023 May 2;175747. doi: 10.1016/j.ejphar.2023.175747.
Jiayan Liu 1,  Tao Mi 1,  Zhaoxia Zhang 1,  Liming Jin 1,  Maoxian Li 1,  Chenghao Zhanghuang 1,  Mujie Li 1,  Jinkui Wang 1,  Xin Wu 1,  Zhaoying Wang 1,  Xiaojun Tan 1,  Zhang Wang 1,  Dawei He 2
Affiliations

Affiliations

  • 1 Department of Urology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing, 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, 400014, PR China.
  • 2 Department of Urology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing, 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, 400014, PR China. Electronic address: [email protected].
PMID: 37142086 DOI: 10.1016/j.ejphar.2023.175747
Abstract

Malignant rhabdomyosarcoma 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 anticipated to give the clinical treatment of MRTK a new direction.

Keywords

Apoptosis; BKM120; Cell phase arrest; MRTK; PI3K/Akt.

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