Department of Urological Surgery, The First Affiliated Hospital, ChongQing Medical University, ChongQing, PR China.
J Exp Clin Cancer Res. 2010 Jun 3;29(1):63. doi: 10.1186/1756-9966-29-63.
in recent years, Livin, a new member of IAPs family, is found to be a key molecule in cancers. Researchers consider Livin may become a new target for tumor therapy; however, the role of it in bladder cancer is still unclear. The purpose of this article is to investigate Antisense Oligonucleotide (ASODN) of Livin on treating bladder cancer cell and underlying mechanisms.
Phosphorathioate modifying was used to synthesize antisense oligonucleotides targeting Livin, followed by transfection into human bladder cancer cell 5637. After transfection, Livin mRNA and protein level, cell proliferation and apoptosis changes, caspase3 level and its effect on human bladder cancer transplantable tumor in nude mice were measured.
results showed Livin ASODN effectively inhibited Livin expression and tumor cell proliferation, and these effects probably through enhanced caspase3 activity and apoptosis of tumor cells. In nude mice transplantable tumor model, Livin expressions were inhibited meanwhile caspase3 expression was increased. Tumor growth slowed down and apoptosis was enhanced.
Our data suggest that Livin plays an important role in inhibiting apoptosis of bladder cancer cells. Livin ASODN may promote cell apoptosis, inhibit bladder cancer growth, and become one of the methods of gene therapy for bladder cancer.
近年来,Livin 作为 IAPs 家族的新成员,被发现是癌症中的关键分子。研究人员认为 Livin 可能成为肿瘤治疗的新靶点;然而,它在膀胱癌中的作用尚不清楚。本文旨在探讨 Livin 的反义寡核苷酸(ASODN)对膀胱癌细胞的治疗作用及其机制。
采用磷硫代修饰合成 Livin 反义寡核苷酸,转染人膀胱癌 5637 细胞。转染后,检测 Livin mRNA 和蛋白水平、细胞增殖和凋亡变化、caspase3 水平及其对裸鼠膀胱癌移植瘤的影响。
结果表明 Livin ASODN 能有效抑制 Livin 表达和肿瘤细胞增殖,其作用可能通过增强 caspase3 活性和肿瘤细胞凋亡实现。在裸鼠移植瘤模型中,抑制 Livin 表达的同时增加 caspase3 表达,肿瘤生长减慢,凋亡增强。
我们的数据表明 Livin 在抑制膀胱癌细胞凋亡中起重要作用。Livin ASODN 可能通过促进细胞凋亡、抑制膀胱癌生长,成为膀胱癌基因治疗的方法之一。