肿瘤坏死因子-α对干扰素-α所致氟尿嘧啶脱氧核苷单磷酸产量增加的抑制作用
Suppressive effect of TNF-alpha on increased production of FdUMP by IFN-alpha.
作者信息
Hatano H, Tanaka N, Naomoto Y, Orita K
机构信息
First Department of Surgery, Okayama University Medical School, Japan.
出版信息
Res Commun Mol Pathol Pharmacol. 1995 Sep;89(3):279-90.
Interferon-alpha (IFN-alpha) exhibits synergistic antitumor activity when combined with tumor necrosis factor-alpha (TNF-alpha) in vitro and in vivo and increases the cytotoxicity of 5-fluorouracil (5-FU) in vitro. Using a colon cancer cell line transplanted into nude mice, we examined the effects of pretreatment for 3 days with IFN-alpha (10(6) IU) and/or TNF-alpha (2.9 x 10(3) JRU) on 5-FU metabolism. 5-FU 30 mg/kg was administered after the pretreatment. IFN-alpha increased the tumor level of 5-fluorodeoxuridine monophosphate (FdUMP), and decreased the free level of thymidylate synthetase. Pretreatment with TNT-alpha alone decreased HUMP whereas TNF-alpha plus IFN-alpha abolished the enhancement of FdUMP production by IFN-alpha. TNF-alpha also suppressed thymidine kinase activity. Neither IFN-alpha nor TNF-alpha altered the incorporation of 5-FU into RNA.
α干扰素（IFN-α）在体外和体内与肿瘤坏死因子-α（TNF-α）联合使用时表现出协同抗肿瘤活性，并且在体外可增强5-氟尿嘧啶（5-FU）的细胞毒性。利用移植到裸鼠体内的结肠癌细胞系，我们研究了用IFN-α（10⁶ IU）和/或TNF-α（2.9×10³ JRU）预处理3天对5-FU代谢的影响。预处理后给予5-FU 30 mg/kg。IFN-α提高了5-氟脱氧尿苷单磷酸（FdUMP）的肿瘤水平，并降低了胸苷酸合成酶的游离水平。单独用TNF-α预处理可降低HUMP，而TNF-α加IFN-α则消除了IFN-α对FdUMP生成的增强作用。TNF-α还抑制胸苷激酶活性。IFN-α和TNF-α均未改变5-FU掺入RNA的情况。
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