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.

为了筛选低氧条件下治疗肝癌的有效药物，本研究在低氧和低氧条件下，检测了抗癌药物对肝癌细胞株PLC/PRF/5和HuH-7的细胞毒作用。在低氧条件下，丝裂霉素C对两种肝癌细胞系的细胞毒性均增强。在缺氧条件下，卡巴醌对单独的PLC/PRF/5显示出增强的细胞毒性。另一方面，阿霉素或顺铂在两种细胞系中都没有细胞毒性增强。因此，肿瘤细胞对细胞毒性剂的敏感性根据肿瘤暴露的条件而改变。因此，化疗药物的选择不仅应取决于个体肿瘤对各种药物的敏感性，而且还应仔细考虑药物在某些条件下细胞毒性的变化。在低氧条件下培养的肝癌细胞株，其通过基质胶包被的滤膜的迁移活性显著增强。此外，这种活性通过暴露于缺氧加上对细胞系的抑制剂而增强得多。这一发现表明，当应用栓塞时，完全杀死癌细胞是重要的。

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》。

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)。

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。

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