肿瘤坏死因子-β抗肿瘤及作用机制的研究

Anti-tumor effects of tumor necrosis factor-β on carcinoma cell lines and its cellular molecular mechanisms

目的 :探讨肿瘤坏死因子 -β(tu mornecrosisfactor β ,TNF β)对 3种人癌细胞的增殖抑制作用及其细胞分子机制。方法 :采用多种体外及体内实验方法 ,从多侧面证实TNF β的抗肿瘤作用。并采用细胞内游离钙浓度测定、12 5I cAMP放免检测法检测cAMP含量。结果 :不同浓度TNF β对肿瘤细胞系均有增殖抑制作用 ,且呈剂量依赖性。当TNF β与顺铂和多柔比星合用 ,JF3 0 5细胞死亡百分比分别达到 ( 68 6±9 0 ) %和 ( 76 5± 7 9) %。TNF β实验组细胞内cAMP浓度明显增加 ,JF3 0 5细胞由( 0 0 5 72± 0 0 176)上升到 ( 0 2 896±0 0 784) pmol/10 6个细胞。此外细胞内钙浓度上升并且凋亡。结论 :TNF β具有体内、外抗肿瘤作用 。

OBJECTIVE:To ascertain the anti-tumor effects of tumor necrosis factor-β on three kinds of human carcinoma cell lines and its mechanisms. METHODS: Several approches and animal experiments were adopted to determine the anticancer effects of tumor necrosis factor-β both in vitro and in vivo in different aspects. In addition,concentration of cytosolic free calcium and cAMP were also tested by using 125Ⅰ-cAMP radioimmunoassay to testify the mechanisms through which tumor necrosis factor-β affected the tumor cell proliferation. RESULTS:Different concentrations of tumor necrosis factor-β had cytotoxicities on these cell lines in a dose dependent pattern. While tumor necrosis factor-β can suppress the expression of PCNA, and the mean weight of tumor was greatly decreased in experimental groups. Its mechanism may be the elevated cAMP level. CONCLUSIONS:Tumor necrosis factor-β has anticancer effects both in vitro and in vivo. Its in vitro mechanism of anticancer effect may be in part by increasing cAMP production and inducing apoptosis.