Ultrasound targeted microbubble destruction for novel dual targeting of HSP72 and HSC70 in prostate cancer.
Ultrasound targeted microbubble destruction for novel dual targeting of HSP72 and HSC70 in prostate cancer.
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超声靶向微泡破坏用于前列腺癌中 HSP72 和 HSC70 的新型双重靶向。
DOI：
10.7314/apjcp.2014.15.3.1285
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Du, Lian-Fang
中科院分区：
文献类型：
--
作者：
Su, Yi-Jin;Liu, Long;Jia, Chao;Du, Lian-Fang
目的：探讨超声靶向微泡破坏(UTMD)是否促进HSP72和HSC70双靶向治疗去势耐药前列腺癌(CRPC)，提高siRNA的特异性和效率，诱导肿瘤细胞特异性凋亡，寻找CRPC特异性的新治疗靶点。用实时定量聚合酶链式反应和Western blotting检测HSP70、HSP90和caspase-3裂解产物的表达。流式细胞仪检测细胞凋亡率和转染率。细胞活性测定用于安全性评价。我们发现HSP72、HSC70和HSP90在正常前列腺上皮细胞(RWPE-1)中不表达或弱表达，而在前列腺癌细胞(VCaP)中均呈强阳性表达。UTMD联合HSP72和HSC70 siRNA的双靶向可提高VCaP细胞的转染率，提高细胞对siRNA的摄取，在mRNA和蛋白水平下调HSP70和HSP90的表达，并诱导广泛的肿瘤特异性细胞凋亡。细胞计数KIT-8检测显示，HSP72/HSC70-siRNA沉默组细胞存活率降低。这些结果表明，UTMD联合双靶向HSP70治疗PCa可能是最有效的，为提高siRNA的特异性和效率，获得最大的治疗效果提供了一种新的、可靠的、非侵入性的、安全的靶向治疗方法。
The aim was to determine whether ultrasound targeted microbubble destruction (UTMD) promotes dual targeting of HSP72 and HSC70 for therapy of castration-resistant prostate cancer (CRPC), to improve the specific and efficient delivery of siRNA, to induce tumor cell specific apoptosis, and to find new therapeutic targets specific of CRPC.VCaP cells were transfected with siRNA oligonucleotides. HSP70, HSP90 and cleaved caspase-3 expression were determined by real-time quantitative polymerase chain reaction and Western blotting. Apoptosis and transfection efficiency were assessed by flow cytometry. Cell viability assays were used to evaluate safety. We found HSP72, HSC70 and HSP90 expression to be absent or weak in normal prostate epithelial cells (RWPE-1), but uniformly strong in prostate cancerous cells (VCaP). UTMD combined with dual targeting of HSP72 and HSC70 siRNA improve the efficiency of transfection, cell uptake of siRNA, downregulation of HSP70 and HSP90 expression in VCaP cells at the mRNA and protein level, and induction of extensive tumor-specific apoptosis. Cell counting kit-8 assays showed decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These results suggest that the combination of UTMD with dual targeting HSP70 therapy for PCa may be most efficacious, providng a novel, reliable, non-invasive, safe targeted approach to improve the specific and efficient delivery of siRNA, and achieve maximal effects.
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DOI：
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