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Combined Treatment with an Oncolytic Adenovirus and Antitumor Activity of Vincristine against Retinoblastoma Cells
Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Department of Biochemistry and Molecular Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 7 June 2012; in revised form: 21 August 2012 / Accepted: 22 August 2012 / Published: 27 August 2012
Abstract: Treatment trends of retinoblastoma (RB) have gradually evolved from eye enucleation and external radiation to local treatment. Combined treatment with an oncolytic virus and chemotherapy is currently a new method in RB treatment. To investigate the therapeutic effect of oncolytic adenovirus SG600 in combination with vincristine (VCR) on retinoblastoma in vitro, the cell viability, cell cycle effects and apoptotic activity of HXO-RB44 cells treated with SG600, VCR or SG600 plus VCR were measured using a cell counting kit-8-based procedure and flow cytometry. Western blot analysis for Akt, p-Akt, p-p53 and p-Rb protein was performed to investigate the underlying mechanisms of combined therapy. The combination therapy exerted a synergistic antitumor effect via a type of G2/M and S phase arrest rather than the induction of apoptosis. The combination of VCR and SG600 further reduced Akt phosphorylation compared with cells treated with VCR alone, suggesting that SG600 could overcome chemoresistance, perhaps by down-regulating Akt in RB cells. An increase in the expression of p-p53 and decrease in p-Rb expression in HXO-RB44 after co-treatment might be associated with cell cycle block. Western blot examination revealed that VCR might enhance SG600 replication. These results suggest that viro-chemo combination therapy is a feasible and potentially promising approach for the treatment of retinoblastoma.
Keywords: retinoblastoma; vincristine; oncolytic adenovirus; Akt; drug resistance
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MDPI and ACS Style
Song, X.; Wang, H.; Jia, R.; Cun, B.; Zhao, X.; Zhou, Y.; Xu, X.; Qian, G.; Ge, S.; Fan, X. Combined Treatment with an Oncolytic Adenovirus and Antitumor Activity of Vincristine against Retinoblastoma Cells. Int. J. Mol. Sci. 2012, 13, 10736-10749.
Song X, Wang H, Jia R, Cun B, Zhao X, Zhou Y, Xu X, Qian G, Ge S, Fan X. Combined Treatment with an Oncolytic Adenovirus and Antitumor Activity of Vincristine against Retinoblastoma Cells. International Journal of Molecular Sciences. 2012; 13(9):10736-10749.
Song, Xin; Wang, Haibo; Jia, Renbing; Cun, Biyun; Zhao, Xiaoping; Zhou, Yixiong; Xu, Xiaofang; Qian, Guanxiang; Ge, Shengfang; Fan, Xianqun. 2012. "Combined Treatment with an Oncolytic Adenovirus and Antitumor Activity of Vincristine against Retinoblastoma Cells." Int. J. Mol. Sci. 13, no. 9: 10736-10749.