Influence of hypoxia on migration potentiality and effect of antitumor drugs in human hepatoma all lines.

缺氧对人肝癌各株系迁移能力及抗肿瘤药物作用的影响。

• 批准号: 03454323
• 负责人: KANEMATSU Takashi
• 金额: $ 0.45万
• 依托单位: NAGASAKI 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: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454323/
• 关键词: hepatocellular carcinoma; hypoxia; chemotherapy; embolization; metastasis; migration activity; hepatoma cell line; antineoplastic agents; 細胞培養; 肝癌; 癌化学療法; 感受性試験; 塞栓療法(TAE); 薬剤選択

In order to select more effective drugs under hypoxia for treatment of hepatocellular carcinoma, the cytotoxicity of antineoplastic agents for two hepatocellular carcinoma cell lines, PLC/PRF/5 and HuH-7, was examined under both oxygenated and hypoxic conditions. Mitomycin C was observed potentially to have enhanced cytotoxicity under hypoxic conditions for both hepatoma cell lines. Carboquone showed enhanced cytotoxicity under hypoxia for PLC/PRF/5 alone. One the other hand, there was no cytotoxic enhancement of adriamycin or cisplatin in either cell line. Thus, the sensitivity of tumor cells to the cytotoxic agents altered according to the conditions to which the tumor was exposed. The selection of the antineoplastic drugs for chemotherapy therefore should depend not only on the sensitivity of individual tumors to various drugs, but the alteration of the cytotoxicity of the drugs under certain conditions should also be carefully taken into account. When hepatoma all line was cultured in hypoxic condition, the migration activity through the filter coated with matrigel was significantly enhanced. Furthermore, this activity was much more enhanced by exposure to hypoxia plus an antineoplastic agent to the cell line. This finding suggests that it is important to kill the cancer cells completely when embolization is applied.

为了选择缺氧条件下更有效的治疗肝细胞癌的药物，在有氧和缺氧条件下考察了抗肿瘤药物对两种肝癌细胞株PLC/PRF/5和HuH-7的细胞毒性。据观察，丝裂霉素 C 在缺氧条件下可能对两种肝癌细胞系具有增强的细胞毒性。卡波醌在缺氧条件下对 PLC/PRF/5 单独表现出增强的细胞毒性。另一方面，阿霉素或顺铂在任一细胞系中均未增强细胞毒性。因此，肿瘤细胞对细胞毒剂的敏感性根据肿瘤暴露的条件而改变。因此，化疗抗肿瘤药物的选择不仅应取决于个体肿瘤对各种药物的敏感性，还应仔细考虑药物在一定条件下细胞毒性的变化。当肝癌全系在低氧条件下培养时，通过涂有基质胶的滤膜的迁移活性显着增强。此外，通过将细胞系暴露于缺氧和抗肿瘤剂，这种活性得到了更大的增强。这一发现表明，在应用栓塞时完全杀死癌细胞非常重要。

项目成果

兼松 隆之 ら: "A comparative study of hepatic resection and trans-catheter arterial embolization for treatment of primary hepatocellular carcinoma" Cancer.

Takayuki Kanematsu 等人：“肝切除术和经导管动脉栓塞治疗原发性肝细胞癌的比较研究”癌症。

山懸 基継: "The difference of antineoplastic agents in chemosensiーtivity of human hepatocellular carcinoma cell line" Europen Journal of Surgical Oncology.

Mototsugu Yamakake：“抗肿瘤药物对人肝细胞癌细胞系化疗敏感性的差异”《欧洲肿瘤外科杂志》。

兼松 隆之: "A comparative study of hepatic resection and transcatheter arterial embolization for treatment of primary hepatoーcelluar carcinoma" Cancer.

Takayuki Kanematsu：“肝切除术和经导管动脉栓塞治疗原发性肝细胞癌的比较研究”癌症。

山懸 基維 ら: "The difference in chemosensitivity to antineoplastic agents of hepatocellular carcinoma cells under normo-oxygenated or hypoxic conditions" European Journal of Surgical Oncology. 18. 379-382 (1992)

Motori Yamakake 等人：“正常氧合或缺氧条件下肝细胞癌细胞对抗肿瘤药物的化学敏感性差异”欧洲肿瘤外科杂志 18. 379-382 (1992)。

Motoyuki Yamagata, Takashi Kanematsu, Takashi Matsumata, Tohru Utsunomiya, Yasuharu Ikeda and Keizo Sugimachi: "The difference in chemosensitivity to antineoplastic agents of human hepatocellular carcinoma cells under normooxygenated or hypoxic conditions

Motoyuki Yamagata、Takashi Kanematsu、Takashi Matsumata、Tohru Utsunomiya、Yasuharu Ikeda 和 Keizo Sugimachi：“常氧或低氧条件下人肝癌细胞对抗肿瘤药物化疗敏感性的差异