Hisaka Toru, Yano Hirohisa, Ogasawara Sachiko, Momosaki Seiya, Nishida Naoyo, Takemoto Yumi, Kojiro Sakiko, Katafuchi Yuno, Kojiro Masamichi
Department of Pathology, Kurume University School of Medicine, Research Center of Innovative Cancer Therapy of the 21 Century COE Program for Medical Science, Kurume University, 67 Asahi-machi, 830-0011 Kurume, Japan.
J Hepatol. 2004 Nov;41(5):782-9. doi: 10.1016/j.jhep.2004.07.012.
BACKGROUND/AIMS: We investigated the effects of consensus interferon (IFN-alphaCon1), a nonnaturally occurring type I interferon with higher specific activity than other type I IFNs, on the growth of human liver cancer cells.
The effect of IFN-alphaCon1 on the proliferation of 13 liver cancer cell lines was investigated in vitro. Hepatocellular carcinoma (HCC) cells (KIM-1 and HAK-1B) were transplanted subcutaneously into the back of nude mice, then IFN-alphaCon1 was subcutaneously administered to the mice once a day for 2 weeks, and tumor volume and histology were examined.
IFN-alphaCon1 expressed a dose-dependent growth inhibitory effect in all cell lines in vitro. KIM-1 tumor volume in mice that received 0.01 microg (10(4)IU)/mouse/day of IFN-alphaCon1 (similar to the clinical dose for chronic hepatitis C) was 62% of the control, 0.1microg/mouse/day resulted in 26%, and 1 microg/mouse/day resulted in 10%. HAK-1B tumor volume under the same treatment was 61, 24 and 0% of the control, respectively. The number of apoptotic cells significantly increased and the number of blood vessels significantly decreased with the increase in IFN-alphaCon1 dose.
IFN-alphaCon1 suppressed HCC growth in nude mice. These data indicate the potential clinical application of IFN-alphaCon1 in the prevention and treatment of HCC.
背景/目的:我们研究了共识干扰素(IFN-αCon1),一种比其他I型干扰素具有更高比活性的非天然存在的I型干扰素,对人肝癌细胞生长的影响。
在体外研究了IFN-αCon1对13种肝癌细胞系增殖的影响。将肝癌细胞(KIM-1和HAK-1B)皮下移植到裸鼠背部,然后每天皮下给予裸鼠IFN-αCon1,持续2周,检查肿瘤体积和组织学。
IFN-αCon1在体外对所有细胞系均表现出剂量依赖性生长抑制作用。接受0.01μg(10⁴IU)/小鼠/天IFN-αCon1(类似于慢性丙型肝炎的临床剂量)的小鼠中,KIM-1肿瘤体积为对照组的62%,0.1μg/小鼠/天导致肿瘤体积为对照组的26%,1μg/小鼠/天导致肿瘤体积为对照组的10%。在相同治疗下,HAK-1B肿瘤体积分别为对照组的61%、24%和0%。随着IFN-αCon1剂量的增加,凋亡细胞数量显著增加,血管数量显著减少。
IFN-αCon1抑制裸鼠肝癌生长。这些数据表明IFN-αCon1在肝癌预防和治疗中的潜在临床应用。