Spontaneous and radiation-induced apoptosis in colorectal carcinoma cells with different intrinsic radiosensitivities:: Survivin as a radioresistance factor
Spontaneous and radiation-induced apoptosis in colorectal carcinoma cells with different intrinsic radiosensitivities:: Survivin as a radioresistance factor
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DOI：
10.1016/s0360-3016(02)04618-7
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发表时间：
2003-04-01
影响因子：
7
通讯作者：
Rödel, F
中科院分区：
文献类型：
--
作者：
Rödel, C;Haas, J;Rödel, F
背景：自发性细胞凋亡已被证明可以预测体内直肠癌对放化疗的反应。然而，哪种基因谱决定了肿瘤是否更倾向于凋亡还是更不倾向于凋亡仍有待阐明。最近，凋亡抑制蛋白家族的一个新成员，命名为生存素，被鉴定。我们探讨了生存的表达对肿瘤细胞凋亡的影响，在三个不同的内在radiosensitivity.Methods和材料：生存蛋白的蛋白表达测定Western印迹分析，和生存mRNA的表达定量TaqMan逆转录聚合酶链反应，无论是在未经处理的细胞和照射后，2和8戈伊。然后将表达谱与自发性和辐射诱导的细胞凋亡相关联（Tunel-测定，DAPI-染色）在低（SW 480）、中等（HCT-15）和高放射敏感性（SW 48）的三种结肠直肠细胞系中，如通过集落形成测定所确定的。体外分析显示，在放射敏感系（SW 48）中，与抗性较强的品系SW 480相比，在Western印迹分析和TaqMan分析中，SW 480的特征在于较高的自发表达和照射后48小时生存素的显著诱导，而生存素表达在未处理时较低，并且在最放射敏感的系SW 48中照射后不增加。HCT-15是中间，无论是相对于Survivin mRNA和蛋白质的表达水平。结论：生存素表达与自发和辐射诱导的细胞凋亡呈负相关，表明生存素是一个重要的抑制凋亡的大肠癌细胞株。因此，分析生存素mRNA或蛋白表达可能提供预测信息的放射性和化疗耐药的个体结直肠肿瘤。(C)2003年爱思唯尔科学公司
Background: Spontaneous apoptosis has been shown to predict tumor response to radiochemotherapy in rectal cancer in vivo. It remains to be elucidated, however, which genetic profile determines whether a tumor is more or less prone to apoptosis. Recently, a novel member of the inhibitor of apoptosis protein family, designated survivin, was identified. We investigated the impact of surviving expression on tumor cell apoptosis in three colorectal cell lines of different intrinsic radiosensitivities.Methods and Materials: Survivin protein expression was measured by Western blot analysis, and survivin mRNA expression by quantitative TaqMan reverse transcription polymerase chain reaction, both in untreated cell and after irradiation with 2 and 8 Gy. The expression profile was then correlated to spontaneous and radiation-induced apoptosis (Tunel-Assay, DAPI-staining) in three colorectal cell lines of low (SW 480), intermediate (HCT-15), and high radiosensitivity (SW 48), as determined by the colony-forming assay.Results: In vitro analysis revealed higher spontaneous and higher radiation-induced apoptosis rates in the radiosensitive line (SW 48), as compared with the more resistant line (SW 480). In Western blot analysis and in TaqMan analysis, SW 480 was characterized by a higher spontaneous expression and a pronounced induction of survivin 48 h after irradiation, whereas survivin expression was low when untreated and not increased after irradiation in the most radiosensitive line SW 48. HCT-15 was intermediate, both with respect to the level of survivin mRNA and protein expression.Conclusion: The inverse correlation of survivin-expression with spontaneous and radiation-induced apoptosis suggests that survivin is an important inhibitor of apoptosis in colorectal cancer cell lines. Analysis of survivin mRNA or protein expression may therefore provide predictive information on radio- and chemoresistance of individual colorectal tumors. (C) 2003 Elsevier Science Inc.