2021 Fiscal Year Final Research Report
Development of a novel therapy targeting liver cancer stem cell-specific RAB3B gene for prevention of postoperative intrahepatic recurrence
Project/Area Number |
19K09218
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Yamaguchi University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
新藤 芳太郎 山口大学, 大学院医学系研究科, 助教 (70749811)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 癌 |
Outline of Final Research Achievements |
To development of targeting therapy against cancer stem-like cells (CSLCs), we examined therapy resistance of CSLCs and identified a responsible gene for the CSLC phenotype. Human hepatoma cell line SK-HEP-1 was used for CSLC induction with a unique medium. To assess the chemoresistance and liver metastasis, MTS assay and splenic injection were performed. Expressional analyses were performed using RNA-seq, qPCR, flow-cytometry, and ELISA. The obtained CSLCs showed increased chemoresistance and metastatic potentials. A RAB3B was identified as an up-regulated gene in both CSLCs and poor prognostic HCCs by RNA-seq. RAB3B-KD cells showed altered CSLC phenotypes such as sphere formation, cell cycle, chemoresistance, and metastatic potentials, and those were rescued by RAB3B complementation. Increased exosome secretion in CSLCs were not observed in the RAB3B-KO cells. It was suggested that the up-regulation of RAB3B plays important roles in CSLCs.
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Free Research Field |
腫瘍学
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Academic Significance and Societal Importance of the Research Achievements |
本研究によって、肝癌幹細胞様細胞 (cancer stem-like sphere cell; CSLC)のsphere形成能、化学療法抵抗性や転移能において、RAB3Bのアップレギュレーションが重要な役割を担っていることが示された。癌の転移・再発において重要な役割を果たす癌幹細胞に対する有望な治療標的としてRAB3Bが有望であることを示唆する学術的・社会的に意義ある成果を得た。
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