Wang Tianyou, Liu Ziqin, Zhang Zhaoxia, Tang Suoqin, Yue Mei, Feng Shunqiao, Hu Mengze, Xuan Litian, Chen Yanfei
Department of Hematology and Oncology, Beijing Children's Hospital, Capital Medicine University, Beijing 100045, P.R. China.
Department of Pediatrics, Capital Institute of Pediatrics, Beijing 100020, P.R. China.
Oncol Lett. 2017 Aug;14(2):2001-2008. doi: 10.3892/ol.2017.6404. Epub 2017 Jun 16.
Survivin has been overexpressed in numerous types of cancer and is associated with a poor clinical outcome. A number of various approaches have been used to counteract survivin in order to inhibit tumor growth or promote cell apoptosis. The present study aimed to evaluate the efficiency and antitumor effect of a survivin-targeted short interfering RNA (siRNA) delivery system using lipid nanoparticles for the treatment of colon cancer. Survivin siRNA (si-survivin) nanoliposomes were prepared and transfected into LoVo cells. The mRNA expression level of survivin was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Cell viability was evaluated by MTT assay. LoVo-bearing nude mice were treated with si-survivin intratumorally or intravenously. Tumor growth in LoVo-bearing mice was monitored and recorded, and tumor samples were obtained for evaluation of survivin expression levels using RT-qPCR, western blotting and immunohischemical staining. The expression level of survivin was significantly reduced by nanoliposomal si-survivin along with cell proliferation inhibition . Intravenous administration of si-survivin nanoliposomes may significantly inhibit tumor growth with less toxicity compared with doxorubicin hydrochloride treatment in LoVo-bearing mice. Nanoliposomal si-survivin may significantly reduce the expression level of survivin and inhibit cell proliferation of colon cancer cells and . si-survivin delivered by lipid nanoparticles may be a potential treatment approach for colon cancer.
生存素在多种癌症中均有过表达,且与临床预后不良相关。为了抑制肿瘤生长或促进细胞凋亡,人们采用了多种方法来对抗生存素。本研究旨在评估一种使用脂质纳米颗粒的靶向生存素的小干扰RNA(siRNA)递送系统治疗结肠癌的效率和抗肿瘤效果。制备了生存素siRNA(si-survivin)纳米脂质体并转染至LoVo细胞。通过逆转录定量聚合酶链反应(RT-qPCR)和蛋白质印迹分析来测定生存素的mRNA表达水平。通过MTT法评估细胞活力。对荷瘤裸鼠进行瘤内或静脉注射si-survivin治疗。监测并记录荷瘤小鼠的肿瘤生长情况,获取肿瘤样本,采用RT-qPCR、蛋白质印迹和免疫组织化学染色法评估生存素表达水平。纳米脂质体si-survivin可显著降低生存素的表达水平,并抑制细胞增殖。与盐酸多柔比星治疗相比,静脉注射si-survivin纳米脂质体对荷瘤裸鼠的肿瘤生长抑制作用显著,且毒性较小。纳米脂质体si-survivin可显著降低生存素的表达水平,抑制结肠癌细胞的细胞增殖。脂质纳米颗粒递送的si-survivin可能是一种潜在的结肠癌治疗方法。