Down-regulation of survivin expression by small interfering RNA induces pancreatic cancer cell apoptosis and enhances its radiosensitivity

被引:43
作者
Hai-Tao Guan
Xing-Huan Xue
Zhi-Jun Dai
Xi-Jing Wang
Ang Li
Zhao-Yin Qin
机构
[1] Xian Jiaotong Univ, Coll Med, Dept Oncosurg, Affiliated Hosp 2, Xian 710004, Shaanxi, Peoples R China
[2] Xian Jiaotong Univ, Coll Med, Affiliated Stomatol Hosp, Xian 710004, Shaanxi, Peoples R China
[3] Xian Jiaotong Univ, Coll Med, Dept Gen Surg, Affiliated Hosp 2, Xian 710004, Shaanxi, Peoples R China
关键词
RNA interference; survivin; pancreatic cancer; radiation;
D O I
10.3748/wjg.v12.i18.2901
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AIM: To investigate the inhibitory effect of small interfering RNA (siRNA) on the expression of survivin in pancreatic cancer cell line PC-2 and the role of siRNA in inducing PC-2 cell apoptosis and enhancing its radiosensitivity. METHODS: A siRNA plasmid expression vector against survivin was constructed and transfected into PC-2 cells with Lipofectamine(TM) 2000. The down regulation of survivin expression was detected by semi-quantitive RT-PCR and immunohistochemical SP method and the role of siRNA in inducing PC-2 cell apoptosis and enhancing its radiosensitivity was detected by flow cytometry. RESULTS: The sequence-specific siRNA efficiently and specifically down-regulated the expression of survivin at both mRNA and protein levels. The expression inhibition ratio was 81.25% at mRNA level detected by semi-quantitive RT-PCR and 74.24% at protein level detected by immunohistochemical method. Forty-eight hours after transfection,apoptosis was induced in 7.03% cells by siRNA and in 14.58% cells by siRNA combined with radiation. CONCLUSION: The siRNA plasmid expression vector against survivin can inhibit the expression of survivin in PC-2 cells efficiently and specifically. Inhibiting the expression of survivin can induce apoptosis of PC-2 cells and enhance its radiosensitivity significantly. RNAi against survivin is of potential value in gene therapy of pancreatic cancer. (C) 2006 The WJG Press. All rights reserved.
引用
收藏
页码:2901 / 2907
页数:7
相关论文
共 37 条
[1]   A role for survivin in radioresistance of pancreatic cancer cells [J].
Asanuma, K ;
Kobayashi, D ;
Furuya, D ;
Tsuji, N ;
Yagihashi, A ;
Watanabe, N .
JAPANESE JOURNAL OF CANCER RESEARCH, 2002, 93 (09) :1057-1062
[2]   Role for a bidentate ribonuclease in the initiation step of RNA interference [J].
Bernstein, E ;
Caudy, AA ;
Hammond, SM ;
Hannon, GJ .
NATURE, 2001, 409 (6818) :363-366
[3]   Expression of the novel inhibitor of apoptosis survivin in normal and neoplastic skin [J].
Chiodino, C ;
Cesinaro, AM ;
Ottani, D ;
Fantini, F ;
Giannetti, A ;
Trentini, GP ;
Pincelli, C .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1999, 113 (03) :415-418
[4]  
Chiou SK, 2003, MED SCI MONITOR, V9, P125
[5]   Use of siRNAs and antisense oligonucleotides against survivin RNA to inhibit steps leading to tumor angiogenesis [J].
Coma, S ;
Noe, V ;
Lavarino, C ;
Adán, J ;
Rivas, M ;
López-Matas, M ;
Pagan, R ;
Mitjans, F ;
Vilaró, S ;
Piulats, J ;
Ciudad, CJ .
OLIGONUCLEOTIDES, 2004, 14 (02) :100-113
[6]   Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells [J].
Elbashir, SM ;
Harborth, J ;
Lendeckel, W ;
Yalcin, A ;
Weber, K ;
Tuschl, T .
NATURE, 2001, 411 (6836) :494-498
[7]   Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans [J].
Fire, A ;
Xu, SQ ;
Montgomery, MK ;
Kostas, SA ;
Driver, SE ;
Mello, CC .
NATURE, 1998, 391 (6669) :806-811
[8]   Argonaute2, a link between genetic and biochemical analyses of RNAi [J].
Hammond, SM ;
Boettcher, S ;
Caudy, AA ;
Kobayashi, R ;
Hannon, GJ .
SCIENCE, 2001, 293 (5532) :1146-1150
[9]   An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells [J].
Hammond, SM ;
Bernstein, E ;
Beach, D ;
Hannon, GJ .
NATURE, 2000, 404 (6775) :293-296
[10]   RNA interference [J].
Hannon, GJ .
NATURE, 2002, 418 (6894) :244-251