Yano Hirohisa, Ogasawara Sachiko, Momosaki Seiya, Akiba Jun, Kojiro Sakiko, Fukahori Suguru, Ishizaki Hironori, Kuratomi Keitaro, Basaki Yuji, Oie Shinji, Kuwano Michihiko, Kojiro Masamichi
Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
Liver Int. 2006 Oct;26(8):964-75. doi: 10.1111/j.1478-3231.2006.01321.x.
We investigated the effects of pegylated IFN-alpha2b (PEG-IFN-alpha2b) on the growth of human liver cancer cells.
The effect of PEG-IFN-alpha2b on the proliferation of 13 liver cancer cell lines was investigated in vitro. Chronological changes in growth and IFN-alpha receptor-2 (IFNAR-2) expression were monitored in hepatocellular carcinoma (HCC) cells (HAK-1B) cultured with PEG-IFN-alpha2b. After HAK-1B cells were transplanted into nude mice, various doses of PEG-IFN-alpha2b or IFN-alpha2b were administered, and tumor volume, weight, histology, and IFNAR-2 expression were examined.
PEG-IFN-alpha2b inhibited the growth of nine cell lines with apoptosis in a dose- and time-dependent manner. Continuous contact with PEG-IFN-alpha2b induced time-dependent growth inhibition and down-regulation of IFNAR-2 expression. PEG-IFN-alpha2b induced a dose-dependent decrease in tumor volume and weight, a significant increase of apoptotic cells, and a decrease in IFNAR-2 expression in the tumor. The clinical dose for chronic hepatitis C was also effective. The antitumor effect of PEG-IFN-alpha2b was significantly stronger than that of non-PEG-IFN-alpha2b in vivo.
Continuous contact with PEG-IFN-alpha2b induces strong antitumor effects and the down-regulation of IFNAR-2 in HCC cells. The data suggest potential clinical application of PEG-IFN-alpha2b for the prevention and treatment of HCC.
我们研究了聚乙二醇化干扰素α2b（PEG-IFN-α2b）对人肝癌细胞生长的影响。
在体外研究PEG-IFN-α2b对13种肝癌细胞系增殖的影响。在用PEG-IFN-α2b培养的肝细胞癌（HCC）细胞（HAK-1B）中监测生长和干扰素α受体2（IFNAR-2）表达的时间变化。将HAK-1B细胞移植到裸鼠体内后，给予不同剂量的PEG-IFN-α2b或IFN-α2b，并检查肿瘤体积、重量、组织学和IFNAR-2表达。
PEG-IFN-α2b以剂量和时间依赖性方式抑制9种细胞系的生长并诱导凋亡。与PEG-IFN-α2b持续接触诱导时间依赖性生长抑制和IFNAR-2表达下调。PEG-IFN-α2b诱导肿瘤体积和重量剂量依赖性降低、凋亡细胞显著增加以及肿瘤中IFNAR-2表达降低。慢性丙型肝炎的临床剂量也有效。在体内，PEG-IFN-α2b的抗肿瘤作用明显强于非PEG-IFN-α2b。
与PEG-IFN-α2b持续接触可诱导肝癌细胞产生强大的抗肿瘤作用并下调IFNAR-2。数据表明PEG-IFN-α2b在预防和治疗肝癌方面具有潜在的临床应用价值。
