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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma.
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Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma.

机译：新型HSP90抑制剂NVP-AUY922对口腔鳞状细胞癌的抗肿瘤作用。

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摘要

Heat-shock protein 90 (HSP90) is a major cellular chaperone protein. HSP90 supports the correct conformation, stabilization, activation, and localization of 'client' oncoproteins, many of which are involved in tumor progression. Therefore, the use of HSP90 inhibitors has become a new strategy in antitumor therapy. However, the effects of an HSP90 inhibitor on oral squamous cell carcinoma are still unclear. NVP-AUY922 (Novartis) is a novel 4,5-diaryloxazole adenosine triphosphate-binding site HSP90 inhibitor. In this study, we investigated the antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma. NVP-AUY922 inhibited the proliferation of oral squamous cell carcinoma cells in vitro. NVP-AUY922 caused degradation of client protein inducing ErbB2, p-Akt, p-S6, hypoxia-inducible factor 1-alpha (HIF1-alpha) and vascular endothelial growth factor (VEGF) and up-regulation of HSP70 in HSC-2 oral squamous cell carcinoma. NVP-AUY922 increased the expression of cleaved caspase-3 and induced apoptosis in HSC-2 cells. Treatment of NVP-AUY922 induced a robust antitumor response and suppressed p-Akt and VEGF expression in an HSC-2 xenograft model. In summary, NVP-AUY922 exhibits in vitro and in vivo efficiency against oral squamous cell carcinoma, representing a promising therapeutic approach for oral squamous cell carcinoma.
机译：热休克蛋白90（HSP90）是一种主要的细胞伴侣蛋白。 HSP90支持“客户”癌蛋白的正确构象，稳定化，激活和定位，其中许多与肿瘤的进展有关。因此，使用HSP90抑制剂已成为抗肿瘤治疗的新策略。但是，尚不清楚HSP90抑制剂对口腔鳞状细胞癌的作用。 NVP-AUY922（Novartis）是新型的4,5-二芳基恶唑三磷酸腺苷结合位点HSP90抑制剂。在这项研究中，我们研究了新型HSP90抑制剂NVP-AUY922对口腔鳞状细胞癌的抗肿瘤作用。 NVP-AUY922在体外抑制口腔鳞状细胞癌细胞的增殖。 NVP-AUY922导致客体蛋白降解，诱导ErbB2，p-Akt，p-S6，缺氧诱导因子1-alpha（HIF1-alpha）和血管内皮生长因子（VEGF）的表达以及HSC-2口服中HSP70的上调鳞状细胞癌。 NVP-AUY922增加了裂解的caspase-3的表达并诱导了HSC-2细胞的凋亡。 NVP-AUY922的治疗在HSC-2异种移植模型中诱导了强大的抗肿瘤反应并抑制了p-Akt和VEGF表达。总之，NVP-AUY922对口腔鳞状细胞癌表现出体外和体内功效，代表了口腔鳞状细胞癌的一种有前途的治疗方法。

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