Regulation of cell growth of hepatoma cells by differentiation inducers and basic investigations for its clinical application

分化诱导剂对肝癌细胞生长的调控及其临床应用基础研究

• 批准号: 04454246
• 负责人: SAITO Hidetsugu
• 金额: $ 4.29万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454246/
• 关键词: hepatoma; differentiation; sodium butyrate; liver-specific antigen; laminin; lymphokine activated killer; nude mouse; 肝癌細胞; 分化; 分化誘導剤; 細胞接着分子; 細胞骨格蛋白; LAK感受性

The possibility of induction of cellular differentiation in human hepatoma cells were investigated. Among the agents investigated, sodium butyrate (SB) is the most possible agent to differentiate human hepatoma cell lines, HCC-T and HCC M.The cell growth, anchorage-dependency and transplantability into a nude mouse of HCC-T and HCC-M were significantly inhibited by SB treatment. The RNA expression of albumin was increased, that of alphafetoprotein was decreased and that of myc was decreased by SB.Some antigen expressions on these cells were changed by SB.The liver-specific antigen which is detected by a mouse monoclonal antibody (H2) was significantly increased by SB treatment. The expression of laminin and fibronectin was significantly decreased and lymphokine-activated killer(LAK)sensitivity was decreased according to the decrease of laminin expression. The decrease of LAK sensitivity was abrogated by anti-laminin. The changes of calcium influx and DNA could not be detected by available instruments. SB did not decrease mitochondrial function and did not induce apoptosis in HCC-T and HCC-M.The in vivo administration of SB (50 mg X 3/nude mouse/w) did not decrease tumor size of transplanted HCC-M cells, although some histological shange was suggested. These results indicate that solid tumors such as hepatoma could be differentiated by SB.SB-treated hepatoma cells functionally came near to hepatocytes and some antigenic shange was induced.

探讨了诱导人肝癌细胞分化的可能性。其中，丁酸钠（SB）是最有可能分化人肝癌细胞系HCC- t和HCC- m的药物，其对HCC- t和HCC- m裸鼠的细胞生长、锚定依赖性和可移植性均有显著抑制作用。SB使白蛋白的RNA表达升高，甲胎蛋白的RNA表达降低，myc的RNA表达降低，并改变了部分抗原在这些细胞上的表达，通过小鼠单克隆抗体（H2）检测到的肝特异性抗原显著升高。层粘连蛋白和纤连蛋白的表达明显降低，淋巴因子激活杀伤因子（LAK）敏感性降低。抗层粘连蛋白消除了LAK敏感性的降低。现有仪器无法检测到钙内流和DNA的变化。SB不降低HCC-T和HCC-M的线粒体功能，也不诱导细胞凋亡。体内给药SB （50 mg x3 /裸鼠/w）没有减少移植HCC-M细胞的肿瘤大小，但有一定的组织学改变。这些结果表明sb可以分化肝癌等实体瘤，sb处理的肝癌细胞在功能上接近肝细胞，并诱导了一定的抗原改变。

项目成果

Hidetsugu Saito and Masaharu Tsuchiya: "Recent advances in the study of hepatocellular carcinoma" Keio J.Med.41. 195-204 (1992)

Hidetsugu Saito 和 Masaharu Tsuchiya：“肝细胞癌研究的最新进展”Keio J.Med.41。

Ayumi Hara, Toshifumi Hibi, Masahiro Yoshioka, Kyoko Toda, Noriaki Watanabe, Atsushi Hayashi, Yasushi Iwao, HidetsuguSaito, Tetsu Watanabe, and Masaharu Tsuchiya: "Changes of proliferativ activity and phenotypes in spontaneous differentiation of a colon c

Ayumi Hara、Toshifumi Hibi、Masahiro Yoshioka、Kyoko Toda、Noriaki Watanabe、Atsushi Hayashi、Yasushi Iwao、Hidetsugu Saito、Tetsu Watanabe 和 Masaharu Tsuchiya：“结肠癌自发分化中增殖活性和表型的变化

Ferdinand M.Guevara et al.: "ヒト肝癌細胞株に対するall-trans retinoic acidの影響" 消化器と免疫. 27. 274-277 (1992)

Ferdinand M.Guevara 等人：“全反式视黄酸对人肝癌细胞系的影响”胃肠病学和免疫学 27. 274-277 (1992)。

Hidetsugu Saito,et al.: "Changes of antigen expression on human hepatoma cell lines caused by Sodium butyrate,a differentiation inducer" J.Gastroenterology. 29. 733-739 (1994)

Hidetsugu Saito 等人：“分化诱导剂丁酸钠引起人肝癌细胞系抗原表达的变化”J.Gastroenterology。

Hidetsugu Saito,et al.: "Visualization of oxidative processes at the cellular level during neutrophil-mediated cytotoxicity against a human hepatoma cell line,HCC-M" Int.J.Cancer. 51. 124-129 (1992)

Hidetsugu Saito 等人：“中性粒细胞介导的针对人肝癌细胞系 HCC-M 的细胞毒性过程中细胞水平氧化过程的可视化”Int.J.Cancer。