UPRES 27-10, Institut Gustave Roussy, Villejuif, France.
Anticancer Res. 2010 Oct;30(10):3869-78.
Oblimersen, an ODN targeting BCL-2 RNA, has been shown to be effective in reducing BCL-2 expression in vitro and in in vivo models engineered to overexpress BCL-2. The present study evaluated the efficacy of combining BCL-2 ODN and radiation in small-cell lung cancers (SCLC) cell lines.
The in vitro effect was determined using short term (cell viability) and long term (clonogenic) assays. Apoptosis, BCL-2 expression and intratumoural uptake of the FAM-ODN with or without prior radiation treatment were also evaluated. Combination of ODN and RT was also assessed in vivo.
Radiation was shown to increase intracellular and intratumoural penetration of oblimersen, confirming previous results obtained in prostate cancer xenograft models. Oblimersen decreased BCL-2 protein expression in vitro and in vivo. BCL-2 ODN sensitised H69 cells to radiation in vitro and in vivo. Oblimersen increased radiation-induced apoptosis and decreased in vivo tumoural vascularisation.
Oblimersen was shown to increase in vitro and in vivo effect of RT on SCLC cell lines. Radiation increases intracellular and intratumoural penetration of ODN. This pre-clinical study argues in favour of clinical development in localised SCLC.
靶向 BCL-2 RNA 的寡核苷酸（ODN）oblimersen 已被证明在体外和体内过表达 BCL-2 的模型中有效降低 BCL-2 的表达。本研究评估了 BCL-2 ODN 与放射治疗联合用于小细胞肺癌（SCLC）细胞系的疗效。
采用短期（细胞活力）和长期（集落形成）测定法来确定体外效果。还评估了凋亡、BCL-2 表达和 FAMA-ODN 在有或没有预先放射治疗下的肿瘤内摄取。还评估了 ODN 和 RT 的联合在体内的效果。
放射治疗被证实可增加 oblimersen 的细胞内和肿瘤内渗透，证实了先前在前列腺癌异种移植模型中获得的结果。oblimersen 在体外和体内降低了 BCL-2 蛋白表达。BCL-2 ODN 可使 H69 细胞在体外和体内对放射治疗敏感。oblimersen 增加了放射诱导的细胞凋亡，并减少了体内肿瘤血管生成。
oblimersen 被证明可增加 SCLC 细胞系的体外和体内放射治疗效果。放射治疗增加了 ODN 的细胞内和肿瘤内渗透。这项临床前研究支持在局部 SCLC 中进行临床开发。
