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富含半胱氨酸的酸性分泌蛋白通过诱导G1期阻滞抑制人胰腺癌细胞的生长。

Secreted protein acidic and rich in cysteine inhibits the growth of human pancreatic cancer cells with G1 arrest induction.

作者信息

Mao Zhengfa, Ma Xiaoyan, Fan Xin, Cui Lei, Zhu Ting, Qu Jianguo, Zhang Jianxin, Wang Xuqing

机构信息

Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China.

出版信息

Tumour Biol. 2014 Oct;35(10):10185-93. doi: 10.1007/s13277-014-2315-0. Epub 2014 Jul 16.

Abstract

Aberrant secreted protein acidic and rich in cysteine (SPARC) expression has been reported to play an important role in the tumor development. However, the pattern and the role of SPARC in pancreatic cancer remain largely unknown. Therefore, we further deciphered the role of SPARC played in pancreatic cancer. We first evaluated the SPARC expression in human pancreatic cancer tissues and pancreatic cancer cells. Then we forced expression and silenced SPARC expression in pancreatic cancer cell lines MIA PaCa2 and PANC-1, respectively, using lentivirus vectors. We characterized the stable cells in vitro. In this study, we found that SPARC expression was weak in cancer cells in specimens which negatively correlated with the expression level of phosphorylated pRB and poorer outcome. Moreover, our results demonstrated that SPARC negatively regulated pancreatic cell growth in vitro. Furthermore, we disclosed that the activation of p53 and p27(Kip1) may involve in the effect of SPARC on pancreatic cancer cells. SPARC is downregulated in pancreatic cancer cells and retards the growth of pancreatic cancer cell. Taken together, these results indicate SPARC may be a potential target for pancreatic cancer therapy.

摘要

据报道,异常分泌的富含半胱氨酸的酸性蛋白(SPARC)表达在肿瘤发展中起重要作用。然而,SPARC在胰腺癌中的模式和作用仍 largely未知。因此,我们进一步解读了SPARC在胰腺癌中所起的作用。我们首先评估了SPARC在人胰腺癌组织和胰腺癌细胞中的表达。然后,我们分别使用慢病毒载体在胰腺癌细胞系MIA PaCa2和PANC-1中强制表达和沉默SPARC表达。我们在体外对稳定细胞进行了表征。在本研究中,我们发现标本中癌细胞中SPARC表达较弱,这与磷酸化pRB的表达水平呈负相关且预后较差。此外,我们的结果表明SPARC在体外对胰腺细胞生长具有负调控作用。此外,我们揭示p53和p27(Kip1)的激活可能参与SPARC对胰腺癌细胞的作用。SPARC在胰腺癌细胞中下调并延缓胰腺癌细胞的生长。综上所述,这些结果表明SPARC可能是胰腺癌治疗的潜在靶点。

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