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首页> 外文期刊>BJU international >Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptor.
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Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptor.

机译:使用靶向1型胰岛素样生长因子受体的反义剂对人前列腺癌进行化学增敏。

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摘要

OBJECTIVE: To assess the effect of the downregulation of type 1 insulin-like growth factor receptor (IGF1R) on the chemosensitivity of prostate cancer cells. IGF1R is overexpressed by prostate cancer compared with benign prostatic epithelium and IGF1R expression commonly persists in androgen-independent metastatic disease at levels comparable to those in the primary. MATERIALS AND METHODS: Human androgen-independent DU145 prostate cancer cells were transfected with IGF1R antisense oligonucleotides or antisense RNA. Transfected cultures were treated with cisplatin, mitoxantrone, paclitaxel or vehicle control, and survival measured using a clonogenic assay. RESULTS: Both antisense strategies suppressed IGF1R protein levels to 30-50% of those in control cultures. This was associated with 1.5-2-fold enhancement of sensitivity to cisplatin, mitoxantrone and paclitaxel, and an increase in cisplatin-induced apoptosis. CONCLUSION: This approach has potential for development as a clinical treatment for advancedprostate cancer and other chemoresistant tumours.
机译:目的:下调1型胰岛素样生长因子受体(IGF1R)对前列腺癌细胞化学敏感性的影响。与良性前列腺上皮相比,IGF1R在前列腺癌中过表达,并且在雄激素非依赖性转移性疾病中,IGF1R的表达通常持续存在,其水平与原发性前列腺癌相当。材料与方法:用IGF1R反义寡核苷酸或反义RNA转染非人类雄激素依赖性DU145前列腺癌细胞。用顺铂,米托蒽醌,紫杉醇或运载体对照处理转染的培养物,并使用克隆形成测定法测定存活率。结果:两种反义策略均可将IGF1R蛋白水平抑制至对照培养物中的30-50%。这与对顺铂,米托蒽醌和紫杉醇的敏感性提高1.5-2倍以及顺铂诱导的细胞凋亡增加有关。结论:该方法具有发展潜力,可作为晚期前列腺癌和其他化学耐药性肿瘤的临床治疗方法。

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