ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2022
BRCA2 deficiency increases sensitivity of medulloblastoma to Olaparib by inhibiting RAD51-mediated DNA damage repair system.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 3 citations in OpenAlex.
- Smyca-FOXM1 ribonucleoprotein complex promotes homologous recombination and tumor immune evasion to define a therapeutic target of triple-negative breast cancer.Journal of biomedical science · 2026Article
- Medulloblastoma in Adolescents and Young Adults (AYA): Bridging Pediatric Paradigms and Adult Oncology Practice.Journal of clinical medicine · 2025Review
- Integrative genomic analysis reveals cancer-associated mutations in patients with ophthalmic tumors.The Journal of international medical research · 2024Article
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Abstract
purposeBRCA2 defect exists in glioma and regulates drug resistance of glioma to chemotherapy. However, its role in medulloblastoma and the mechanism is not known. To investigate the effects of BRCA2 deficiency combined with Olaparib in medulloblastoma and the mechanism.
methodsBRCA2 was knocked down by RNAi technology and cell proliferation was detected by CCK-8 assay. Cell apoptosis was determined by FACS analysis when the in vivo role of BRCA2 was explored with xenograft mice model. Western blotting technology was used to explore the mechanism of BRCA2.
resultsKnockdown of BRCA2 enhanced the inhibitory effect of Olaparib on proliferation of Daoy and LN229 cells. The inhibition rate of Olaparib on Daoy or LN229 cells was 61.1%, 66.03% in shBRCA2 group, while it was 42.9%, 41.1% in shNC group. Overexpression of RAD51 partially reversed the effect of shBRCA2. In Daoy cells, apoptotic rate was 26.9% in Olaparib group and 58.9% in Olaparib/shBRCA2 group. However, it was 33.4% after RAD51 was overexpressed. It was the same in LN229 cells. In xenograft mice model, tumor volume in Olaparib and Olaparib/shBRCA2 group was 376.12 and 84.95mm
conclusionsKnockdown of BRCA2 increases the sensitivity of medulloblastoma cells to Olaparib and strengthens the efficacy of Olaparib in vitro and in vivo. Knockdown of BRCA2 causes DNA damage repair by regulating RAD51-mediated signaling pathway in Daoy cells.
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