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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Inhibition of BCL-2 in small cell lung cancer cell lines with oblimersen, an antisense BCL-2 oligodeoxynucleotide (ODN): in vitro and in vivo enhancement of radiation response.
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Inhibition of BCL-2 in small cell lung cancer cell lines with oblimersen, an antisense BCL-2 oligodeoxynucleotide (ODN): in vitro and in vivo enhancement of radiation response.

机译：用奥利默森（一种反义BCL-2寡脱氧核苷酸（ODN））抑制小细胞肺癌细胞系中的BCL-2：体内和体外放射反应的增强。

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BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
机译：背景：Oblimersen是一种靶向BCL-2 RNA的ODN，已被证明可有效降低BCL-2的体外表达，并在设计为过表达BCL-2的体内模型中有效。本研究评估了在小细胞肺癌（SCLC）细胞系中结合BCL-2 ODN和放射线的功效。材料与方法：使用短期（细胞生存力）和长期（克隆形成）测定法确定体外作用。还评估了有无放射治疗后FAM-ODN的凋亡，BCL-2表达和肿瘤内摄取。还在体内评估了ODN和RT的组合。结果表明，辐射增加了奥利默森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在体内外均降低BCL-2蛋白表达。 BCL-2 ODN使H69细胞在体外和体内对放射线敏感。 Oblimersen增加了辐射诱导的细胞凋亡，并降低了体内肿瘤血管生成。结论：Oblimersen已被证明可增强RT对SCLC细胞系的体外和体内作用。辐射增加了ODN在细胞内和肿瘤内的渗透。这项临床前研究主张局部SCLC的临床开发。

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