Combined treatment with an oncolytic adenovirus and antitumor activity of vincristine against retinoblastoma cells.

Combined treatment with an oncolytic adenovirus and antitumor activity of vincristine against retinoblastoma cells.
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溶瘤腺病毒与长春新碱联合治疗视网膜母细胞瘤细胞

DOI:
10.3390/ijms130910736
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发表时间:
2012
影响因子:
5.6
通讯作者:
Fan X
Fan X
中科院分区:
生物学2区
文献类型:
--
作者:
Song X;Wang H;Jia R;Cun B;Zhao X;Zhou Y;Xu X;Qian G;Ge S;Fan X

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视网膜母细胞瘤(retinoblastoma, RB)的治疗趋势已逐渐从眼球去核和外照射发展到局部治疗。溶瘤病毒联合化疗是目前治疗RB的一种新方法。为了研究溶瘤腺病毒SG600联合长春新碱(VCR)对体外视网膜母细胞瘤的治疗效果,采用细胞计数试剂盒-8和流式细胞术检测了SG600、VCR或SG600加VCR对hro - rb44细胞的细胞活力、细胞周期效应和凋亡活性。Western blot分析Akt、p-Akt、p-p53和p-Rb蛋白,探讨联合治疗的潜在机制。联合治疗通过G2/M期和S期阻滞而不是诱导细胞凋亡发挥协同抗肿瘤作用。与单独使用VCR处理的细胞相比,VCR和SG600联合使用进一步降低了Akt的磷酸化水平,这表明SG600可能通过下调RB细胞中的Akt来克服化疗耐药。HXO-RB44共处理后p-p53表达升高,p-Rb表达降低,可能与细胞周期阻滞有关。Western blot检测显示VCR可增强SG600的复制。这些结果表明,病毒化疗联合治疗是一种可行的、有潜力的治疗视网膜母细胞瘤的方法。
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.
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