Wu Zhuo, Zeng Yanyan, Zhong Mingkang, Wang Bin
Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
Department of Pharmacy, Teaching Hospital of Fujian Medical University, Quanzhou Women's and Children's Hospital, Quanzhou, Fujian 362000, P.R. China.
Mol Med Rep. 2014 May;9(5):1787-93. doi: 10.3892/mmr.2014.2023. Epub 2014 Mar 6.
Lung cancer is the major cause of cancer-associated mortality worldwide and the invasive and metastatic characteristics of lung tumor cells are responsible for their high malignancy. Protease-activated receptor 1 (PAR1) is a G-protein-coupled receptor (GPCR) which is activated by a unique proteolytic mechanism. PARs have crucial roles in hemostasis and thrombosis as well as tumor progression. RNA interference (RNAi) is a fundamental cellular mechanism for gene silencing that is able to be harnessed for the development of novel anti-cancer drugs. In the present study, PAR1 was successfully inhibited by using Lipofectamine RNAiMAX transfection reagent to deliver siRNA. Inhibition occurred at the mRNA and protein level as determined by polymerase chain reaction and western blot analysis. Furthermore, the growth and invasion of tumor cells were significantly decreased. In conclusion, the present study demonstrated that the progression of A549 cells is able to be inhibited by knockdown of PAR1 expression. Efficient delivery of the specific siRNA targeting PAR1 may be used for further study in clinical cancer therapy.
肺癌是全球癌症相关死亡的主要原因,肺肿瘤细胞的侵袭和转移特性导致其高度恶性。蛋白酶激活受体1(PAR1)是一种G蛋白偶联受体(GPCR),通过独特的蛋白水解机制被激活。PARs在止血、血栓形成以及肿瘤进展中起关键作用。RNA干扰(RNAi)是一种基因沉默的基本细胞机制,可用于开发新型抗癌药物。在本研究中,使用Lipofectamine RNAiMAX转染试剂递送siRNA成功抑制了PAR1。通过聚合酶链反应和蛋白质印迹分析确定,在mRNA和蛋白质水平均发生了抑制。此外,肿瘤细胞的生长和侵袭明显减少。总之,本研究表明,敲低PAR1表达能够抑制A549细胞的进展。靶向PAR1的特异性siRNA的有效递送可用于临床癌症治疗的进一步研究。