Alternative Titleスルフォラファンの肝癌発育抑制効果および血管新生抑制効果に関する基礎的検討
Periodical titleArchives in cancer research
Note (General)type:Thesis
Sulforaphane (SFN) exhibits inhibitory effects in different types of cancers. However, its inhibitory effect on liver cancer remains unknown. This study aimed to determine the therapeutic potential of SFN for the treatment of liver cancer and explore the functional mechanisms underlying the inhibitory effects of SFN. Water-Soluble Tetrazolium salt (WST-1) assay was performed to assess the in vitro effect of SFN on cell proliferation in the human liver cancer cell lines, HepG2 and Huh-7. The mRNA levels of Nrf2 target genes and cell cycle-related genes were determined using quantitative RT-PCR. For assessing the inhibitory effect of SFN in vivo, we injected immortalized liver cancer cells into BALB/c nude mice as a xenograft model. SFN was orally administrated daily after tumor inoculation and continued for thirty-five days until their sacrifices. Nrf2 activation, induced by SFN, was confirmed by mRNA upregulation of HO-1, MRP2, and NQO1 in both the cell lines. Significant inhibition of liver cancer cell proliferation by SFN was shown in vitro in a dose-dependent manner by the downregulation of CCND1, CCNB1, CDK1 and CDK2. In in vivo studies, the administration of SFN significantly reduced the subcutaneous tumor burdens at the end of experiments by suppressing tumor cell proliferation, confirmed by Ki67 immunohistochemical analysis. The mRNA levels of CCND1, CCNB1, CDK1 and CDK2 were also decreased in these SFNtreated xenograft tumors. Moreover, CD34 immunostaining elucidated that the intratumoral neovascularization was markedly attenuated in the SFN-treated xenograft tumors. SFN exerts inhibitory effect on human liver cancer cells with antiangiogenic activity. The earlier version of this study was presented at the meeting of AASLD Liver Learning on Oct 2017.
博士（医学）・甲第707号・平成31年3月15日
© The Author(s) 2018 Under License of Creative Commons Attribution 3.0 License https://creativecommons.org/licenses/by/3.0/
identifier:Archives in cancer research Vol.6 No.4 Article No.23 (2018 Dec)
identifier:22546081
identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3555
identifier:Archives in cancer research, 6(4): Article No.23
DOIinfo:doi/10.21767/2254-6081.100189
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2019-07-05T01:13:02+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション