Antitumor effects of human ribonuclease inhibitor gene transfected on B16 melanoma cell
Antitumor effects of human ribonuclease inhibitor gene transfected on B16 melanoma cell
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DOI：
10.1016/j.biocel.2004.11.020
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发表时间：
2005-06-01
影响因子：
4
通讯作者：
Cui, XY
中科院分区：
文献类型：
--
作者：
Chen, JX;Gao, Y;Cui, XY
人核糖核酸酶抑制因子（RI）是一种细胞质酸性蛋白。实验证明，它能有效抑制肿瘤诱导的血管生成，抑制肿瘤生长。核糖核酸酶抑制因子几乎完全由富含亮氨酸的重复序列构成，除了抑制核糖核酸酶A和血管生成素活性外，可能还参与未知的生物学效应。核糖核酸酶抑制剂抗肿瘤的确切分子机制目前尚不清楚。为了进一步了解核糖核酸酶抑制因子的功能及其与肿瘤生长的关系，本研究建立了利用逆转录病毒包装细胞系PA317将人核糖核酸酶抑制因子cDNA转染小鼠B16细胞的方法。鉴定了用核糖核酸酶抑制剂稳定高表达转染的细胞系。体外实验发现，转染核糖核酸酶抑制因子的质粒能明显抑制细胞增殖，调节细胞周期，诱导细胞凋亡。转染RI cDNA的B 16细胞注射组肿瘤生长明显受到抑制，肿瘤重量减轻，微血管密度降低，潜伏期延长，存活时间延长。上述结果揭示了核糖核酸酶抑制剂抗肿瘤作用的新机制，即除抗血管生成外，还与诱导细胞凋亡、调节细胞周期和抑制细胞增殖有关。这些结果提示，核糖核酸酶抑制因子可能是某些组织中肿瘤抑制基因的候选基因。RI可作为基因治疗的靶基因。我们的研究可能具有生物学和临床意义。(c)2004爱思唯尔有限公司保留所有权利。
Human ribonuclease inhibitor (RI) is a cytoplasmic acidic protein. The experiment demonstrated that it might effectively inhibit tumor-induced angiogenesis and inhibit tumor growth. Ribonuclease inhibitor is constructed almost entirely of leucine-rich repeats, which might be involved in unknown biological effects besides inhibiting RNase A and angiogenin activities. The exact molecular mechanism of antitumor on ribonuclease inhibitor remains unclear so far. In order to further understand the function of ribonuclease inhibitor and investigate the relationship with tumor growth, our study established a transfection of human ribonuclease inhibitor cDNA into the murine B16 cells by the retroviral packaging cell line PA317. The cell line transfected with a stably high expression of ribonuclease inhibitor was identified. We found that the transfected ribonuclease inhibitor could obviously inhibit cell proliferation, regulate cell cycle and induce cell apoptosis in vitro. Mice that were injected with the B 16 cells transfected RI cDNA showed a significant inhibition of the tumor growth with lighter tumor weight, lower density of microvessels, longer latent periods, and survival time than those in the other two control groups. In conclusion, the results reveal the novel mechanism that antitumor effect of ribonuclease inhibitor is also associated with inducing apoptosis, regulating cell cycle and inhibiting proliferation besides antiangiogenesis. These results suggest that ribonuclease inhibitor might be a candidate of tumor suppressor gene in some tissues. RI could become a target gene for gene therapy. Our study may be of biological and clinical importance. (c) 2004 Elsevier Ltd. All rights reserved.