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Báo cáo hóa học: " HSF1 overexpression enhances oncolytic effect of replicative adenovirus"

HSF1 overexpression enhances oncolytic effect of replicative adenovirus | Wang et al. Journal of Translational Medicine 2010 8 44 http www.translational-medicine.eom content 8 1 44 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access HSF1 overexpression enhances oncolytic effect of replicative adenovirus Cheng Wang 1 4 Zhehao Daif2 Rong Fan 3 Youwen Deng2 Guohua Lv2 and Guangxiu Lu 1 Abstract Background E1B55kD deleted oncolytic adenovirus was designed to achieve cancer-specific cytotoxicity but showed limitations in clinical study. To find a method to increase its efficacy we investigated the correlation between oncolytic effect of such oncolytic adenovirus Adel55 and intracellular heat shock transcription factor 1 HSF1 activity. Methods In the present study human breast cancer cell line Bcap37 was stably transfected with constitutively active HSF1 cHSF1 or HSF1 specific siRNA HSF1i to establish increased or decreased HSF1 expression levels. Cytotoxicity of Adel55 was analyzed in these cell lines in vitro and in vivo. Furthermore Adel55 incorporated with cHSFI Adel55-cHSF1 was used to treat various tumor xenografts. Results Adel55 could achieve more efficient oncolysis in cHSFI transfected Bcap37 cells both in vitro and in vivo. However inhibition of HSF1 expression by HSF1i could rescue Bcap37 cell line from oncolysis by Adel55. A time course study of viral replication established a correlation between higher replication of Adel55 and cytolysis or tumor growth inhibition. Then we constructed Adel55-cHSF1 for tumor gene therapy and demonstrated that it is more potent than Adel55 itself in oncolysis and replication in both Bcap37 and SW620 xenografts. Conclusions cHSF1 enhances the Adel55 cell-killing potential through increasing the viral replication and is a potential therapeutic implication to augment the potential of E1B55kD deleted oncolytic adenovirus by increasing its burst. Background Oncolytic adenoviruses are a class of promising anticancer agents which are designed to selectively replicate in tumor cells and lead to .