Adenovirus-mediated transfer of siRNA against survivin enhances the radiosensitivity of human non-small cell lung cancer cells.
Expression of survivin has been reported to be correlated with shorter survival in patients with non-small cell lung cancer (NSCLC), and overexpression of survivin may lead to radioresistance in various human cancers. In this study, we inhibited survivin expression by using an adenoviral vector (AdsiSurvivin)-mediated RNA interference to elucidate the combined effect of survivin-targeting gene therapy and radiotherapy on the NSCLC cells. Our data showed that AdsiSurvivin exerted survivin gene silencing, induced apoptosis, and significantly attenuated the growth potential in NSCLC cells within 72 h after infection. The combined treatment modalities with AdsiSurvivin infection and radiation were significantly more potent on cell-growth inhibition than monotherapy. In H1650, H460, A549, and H1975 human NSCLC cells, the survival ratios of AdsiSurvivin-treated groups at multiplicity of infection of 25 and 50 were significantly lower than those of control groups at varying radiation dose (0-8 Gy; three-way analysis of variance, P<0.05). The cytotoxicity of combined AdsiSurvivin infection and irradiation increased in a dose-dependent manner in both the virus and the irradiation treatment. Knockdown of the survivin gene expression seems to be a promising treatment strategy for NSCLC. Our data warrant the need for further effort to develop survivin-targeted radiosensitizer for lung cancer treatment.
Yang
C-T
CT
Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan. yang1946@cgmh.org.tw
Li
J-M
JM
Weng
H-H
HH
Li
Y-C
YC
Chen
H-C
HC
Chen
M-F
MF
D000256:Adenoviridae / Q000235:genetics*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000532:radiotherapy*; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D000077022:Survivin