Transcriptome sequencing analysis revealed the molecular mechanism of BNCT inhibiting the growth of U87 subcutaneous tumor
摘要
BNCT is known as the “fifth therapy” after surgery, traditional radiotherapy, anti-cancer drugs and immunotherapy. It has prominent clinical advantages for brain tumors.
PurposeThe aim of this study is to reveal the underlying mechanism of BNCT in the treatment of glioblastoma through transcriptome analysis, and to provide new theoretical basis and potential therapeutic targets for its clinical application.
MethodsThe neutron beam was derived from Mazu Branch of the Union Hospital Affiliated to Fujian Medical University. Human glioma cell lines U87 was used to evaluate the cytotoxicity of BNCT. U87 tumor-bearing mice were divided into four groups: Control (untreated); N20 (neutron irradiation only); BPA (500 mg/kg BPA only); and 500N20 (500 mg/kg BPA plus neutron irradiation). Transcriptome sequencing was used to analyze gene expression profiles, functional enrichment pathways and key regulatory networks after BNCT treatment.
Results500N20 has obvious inhibitory effect on U87 subcutaneous tumor. GO and KEGG functional enrichment analysis showed that tumors after BNCT were significantly enriched in cell cycle and cell death pathways. Three cell cycle-related genes FANCI, UHRF1 and BEX2 related to the prognosis of glioma were screened out. In addition, BNCT promotes apoptosis, inhibits ferroptosis, and induces exogenous apoptosis induced by the death receptors FAS and TNFRSF10B.
ConclusionBNCT induced cell cycle changes associated with prognostic genes FANCI, UHRF1 and BEX2. BNCT induces extrinsic apoptosis mainly through the pathway of death receptors such as FAS and TNFRSF10B. This study provides potential therapeutic targets and theoretical basis for BNCT clinical treatment of glioma.