分子伴侣热休克蛋白90(heat shock protein 90,HSP90)能够通过泛素化途径保护细胞内蛋白质功能,其在肿瘤细胞中呈过表达状态,维持肿瘤细胞生长、增殖、抗凋亡及转移能力。Ganetespib是目前广泛应用于多种肿瘤治疗临床试验的小分子HSP90...分子伴侣热休克蛋白90(heat shock protein 90,HSP90)能够通过泛素化途径保护细胞内蛋白质功能,其在肿瘤细胞中呈过表达状态,维持肿瘤细胞生长、增殖、抗凋亡及转移能力。Ganetespib是目前广泛应用于多种肿瘤治疗临床试验的小分子HSP90抑制剂,其单药具有高效能的抗肿瘤活性,联合用药能增强标准化疗或其他靶向治疗疗效,且能同时克服多种肿瘤的耐药机制,本文就Ganetespib在多种人类恶性实体肿瘤治疗中的疗效进行讨论。展开更多
目的体外探讨热休克蛋白90(heat shock protein 90,HSP90)抑制剂Ganetespib对PC12细胞生长的影响及血管内皮生长因子VEGF表达的调控。方法应用噻唑蓝(MTT)比色法观察Ganetespib对大鼠嗜铬细胞瘤细胞系PC12细胞的生长抑制作用;流式细胞...目的体外探讨热休克蛋白90(heat shock protein 90,HSP90)抑制剂Ganetespib对PC12细胞生长的影响及血管内皮生长因子VEGF表达的调控。方法应用噻唑蓝(MTT)比色法观察Ganetespib对大鼠嗜铬细胞瘤细胞系PC12细胞的生长抑制作用;流式细胞学技术观察不同浓度Ganetespib处理细胞后的细胞周期变化;蛋白质免疫印迹法(Western blotting法)检测HSP90、VEGF蛋白的表达变化。结果 Ganetespib呈时间、剂量依赖性抑制PC12细胞,24h半数抑制浓度(IC50)为0.2μmol/L;Ganetespib在0.2μmol/L浓度能够有效引起PC12细胞周期阻滞于G0/G1期;Ganetespib能抑制PC12细胞的HSP90、VEGF的表达。结论 HSP90抑制剂Ganetespib能抑制PC12细胞增殖,诱导细胞周期阻滞,抑制HSP90、VEGF蛋白表达。展开更多
Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting ...Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting the apoptotic signal, reducing the expression of apoptotic proteins and/or amplifying survival signals through increased production of antiapoptotic molecule. This review describes associations between heat shock proteins （HSPs） and the human androgen receptor （AR）, the role of HSPs and other stress-induced proteins in PCa development and emerging strategies in targeting these protective proteins to treat PCa.展开更多
文摘分子伴侣热休克蛋白90(heat shock protein 90,HSP90)能够通过泛素化途径保护细胞内蛋白质功能,其在肿瘤细胞中呈过表达状态,维持肿瘤细胞生长、增殖、抗凋亡及转移能力。Ganetespib是目前广泛应用于多种肿瘤治疗临床试验的小分子HSP90抑制剂,其单药具有高效能的抗肿瘤活性,联合用药能增强标准化疗或其他靶向治疗疗效,且能同时克服多种肿瘤的耐药机制,本文就Ganetespib在多种人类恶性实体肿瘤治疗中的疗效进行讨论。
文摘Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting the apoptotic signal, reducing the expression of apoptotic proteins and/or amplifying survival signals through increased production of antiapoptotic molecule. This review describes associations between heat shock proteins （HSPs） and the human androgen receptor （AR）, the role of HSPs and other stress-induced proteins in PCa development and emerging strategies in targeting these protective proteins to treat PCa.
