Ikeguchi M, Liu J, Kaibara N
First Department of Surgery, Faculty of Medicine, Tottori University, Yonago, Japan.
Apoptosis. 2002 Feb;7(1):23-9. doi: 10.1023/a:1013556727182.
Survivin is a member of the inhibitor of apoptosis protein (IAP) family. Survivin has been reported to be expressed in many cancers, but not in differentiated normal tissue. Recent studies revealed that survivin correlated with the chemo-resitance of cancer cells. In the present study, the changes in expression levels of survivin messenger RNA (mRNA) and survivin protein in a gastric cancer cell line (MKN-45) during cisplatin (CDDP) treatment were analyzed and compared with the occurrence of apoptotic cell death. Cell growth was inhibited even with a low dose CDDP (0.1 or 1 microg/ml) 1 hr treatment. However, the percentage of apoptotic cells did not change after 48 hr incubation with low dose CDDP. Only with high dose CDDP (10 microg/ml), did the percentage of apoptotic cells explosively increase between 12 and 24 hr treatment. Relative expression levels of survivin mRNA and survivin protein increased after CDDP treatment. The cell expression rates of survivin mRNA after 48 hr treatment with 0.1 and 1 microg/ml of CDDP were 2 to 6 fold higher than that of the survivin mRNA of untreated cells. Also, the relative cell expression level of survivin protein after 24 hr treatment with 0.1 or 1 microg/ml of CDDP was 3 to 6.5 fold higher than that of the survivin protein of untreated cells. These results indicate that survivin expression may correlate with the chemo-resistance of malignant cells.
生存素是凋亡抑制蛋白（IAP）家族的成员。据报道，生存素在许多癌症中表达，但在分化的正常组织中不表达。最近的研究表明，生存素与癌细胞的化疗耐药性相关。在本研究中，分析了顺铂（CDDP）处理期间胃癌细胞系（MKN-45）中生存素信使核糖核酸（mRNA）和生存素蛋白表达水平的变化，并与凋亡细胞死亡的发生情况进行了比较。即使低剂量CDDP（0.1或1微克/毫升）处理1小时，细胞生长也受到抑制。然而，低剂量CDDP孵育48小时后，凋亡细胞的百分比没有变化。仅高剂量CDDP（10微克/毫升）处理12至24小时后，凋亡细胞的百分比才急剧增加。CDDP处理后，生存素mRNA和生存素蛋白的相对表达水平升高。用0.1和1微克/毫升CDDP处理48小时后，生存素mRNA的细胞表达率比未处理细胞的生存素mRNA高2至6倍。此外，用0.1或1微克/毫升CDDP处理24小时后，生存素蛋白的相对细胞表达水平比未处理细胞的生存素蛋白高3至6.5倍。这些结果表明，生存素表达可能与恶性细胞的化疗耐药性相关。
