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首页> 外文会议>International symposium on controlled release of bioactive materials;Consumer and diversified products conference >Enhanced therapeutic efficacy of bcl-2antisense oligonucleotide G3139 combined with sterically-stabilized liposomal doxorubicin
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Enhanced therapeutic efficacy of bcl-2antisense oligonucleotide G3139 combined with sterically-stabilized liposomal doxorubicin

机译：bcl-2反义寡核苷酸G3139与空间稳定的脂质体阿霉素联用可提高治疗效果

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摘要

Bcl-2 is a key apoptosis-regulating protein that has been implicated in mechanisms of chemoresistance in cancer~1. As most antitumor agents elicit their cytotoxic action via apoptosis, combining anticancer drugs with Bcl-2 antisense oligonucleotides (AS ODN) provides an attractive therapeutic strategy to overcome drug resistance in cancer cells, by increaisng their sensitivity to chemotherapeutics like doxorubicin (DOX). Given that free DOX (F-DOX) has a short plasma half-life, DOX was encapsulated in sterically-stabilized liposomes (SL-DOX)~2 where it was predicted that liposome-mediated changes in the drug pharmacokinetics could increase circulation longevity and passive targeting into solid tumors, thus exposing tumor cells to higher levels of drug. The objective of this study was to characterize the molecular and pharmacological effects of Bcl-2 AS G3139 alone and in combination with F-DOX or SL-DOX in a Bcl-2-expressing human breast solid tumor (MDA435/LCC6) xenograft model in SCID mice. In addition, we utilized these two DOX formulations combined with G3139 to investigate the effect drug pharmaco-distribution may have on the antitumor activity.
机译：Bcl-2是一种重要的凋亡调控蛋白，与癌症〜1的化学耐药机制有关。由于大多数抗肿瘤药物通过凋亡引发细胞毒性作用，因此，将抗癌药物与Bcl-2反义寡核苷酸（AS ODN）结合使用，可以通过增加其对阿霉素（DOX）等化学疗法的敏感性来克服癌细胞的耐药性，从而提供了一种有吸引力的治疗策略。鉴于游离DOX（F-DOX）的血浆半衰期短，将DOX封装在空间稳定的脂质体（SL-DOX）〜2中，据推测脂质体介导的药物药代动力学变化可增加循环寿命和被动靶向实体瘤，从而使肿瘤细胞暴露于更高水平的药物中。这项研究的目的是表征Bcl-2 AS G3139单独和与F-DOX或SL-DOX一起在表达Bcl-2的人乳腺实体瘤（MDA435 / LCC6）异种移植模型中的分子和药理作用。 SCID小鼠。此外，我们将这两种DOX制剂与G3139结合使用，以研究药物药理分布对抗肿瘤活性的影响。

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