Abstract
AbstractExpression 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 RNAi to elucidate the combined effect of survivin-targeting gene therapy and radiotherapy on the NSCLC cells. Our data revealed that AdsiSurvivin exerted survivin gene silencing, induced apoptosis, and significantly attenuated the growth potential in NSCLC cells within 72 hours 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 m.o.i. of 25 and 50 were significantly lower than those of control groups at varying radiation dose (0~8 Gy; three-way ANOVA, 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 appears to be a promising treatment strategy for NSCLC. Our data warrants the need for further effort to develop survivin-targeted radiosensitizer for lung cancer treatment.
Highlights
Survivin is a member of the inhibitor of apoptosis family (IAP) that acts as a suppressor of apoptosis and plays a critical role in tumor initiation, progression, and drug resistance.[1]
The conventional chemotherapy regimens and radiotherapy are more of a hindrance due to their limited efficacy, significant toxicity, the development of resistance and high relapse rates; this warrants the need for newer therapeutic approaches
Due to the high expression level in non-small cell lung cancer (NSCLC) and significant clinical association with survival outcome and treatment resistance, survivin has been widely evaluated as a potential therapeutic target for radiation sensitization in lung cancer
Summary
Survivin is a member of the inhibitor of apoptosis family (IAP) that acts as a suppressor of apoptosis and plays a critical role in tumor initiation, progression, and drug resistance.[1]. Increasing evidences indicated that the expression of survivin correlated with radioresistance in various cancers, thereby implying that survivin may be a potential target for radiosensitization during cancer treatment.[11,12,13,14]
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