Chen Shu-Dong, Song Mao-Min, Zhong Zhi-Qiang, Li Na, Wang Pi-Lin, Cheng Shi, Bai Ri-Xing, Yuan Hui-Sheng
Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Asian Pac J Cancer Prev. 2012;13(3):753-9. doi: 10.7314/apjcp.2012.13.3.753.
Radixin, encoded by a gene on chromosome 11, plays important roles in cell motility, invasion and tumor progression. However, its function in pancreatic cancer remains elusive. In this study, radixin gene expression was suppressed with a lentivirus-mediated short-hairpin RNA (shRNA) method. We found that radixin shRNA caused down-regulation of radixin in PANC-1 cells, associated with inhibition of pancreatic cancer cell proliferation, survival, adhesion and invasive potential in vitro. When radixin-silenced cells were implanted in nude mice, tumor growth and microvessel density were significantly inhibited as compared to blank control cells or nonsense shRNA control cells. Thrombospondin-1 (TSP-1) and E-cadherin were up-regulated in radixin-silenced PANC-1 cells. Our results suggest that radixin might play a critical role in pancreatic cancer progression, possibly through involvement of down-regulation of TSP-1 and E-cadherin expression.
由11号染色体上的一个基因编码的根蛋白,在细胞运动、侵袭和肿瘤进展中发挥重要作用。然而,其在胰腺癌中的功能仍不清楚。在本研究中,采用慢病毒介导的短发夹RNA(shRNA)方法抑制根蛋白基因表达。我们发现,根蛋白shRNA导致PANC-1细胞中根蛋白下调,与体外抑制胰腺癌细胞增殖、存活、黏附和侵袭潜能相关。当将根蛋白沉默的细胞接种到裸鼠体内时,与空白对照细胞或无义shRNA对照细胞相比,肿瘤生长和微血管密度受到显著抑制。血小板反应蛋白-1(TSP-1)和E-钙黏蛋白在根蛋白沉默的PANC-1细胞中上调。我们的结果表明,根蛋白可能在胰腺癌进展中起关键作用,可能是通过下调TSP-1和E-钙黏蛋白的表达来实现的。