靶向 HSP70-E7 相互作用的 SHetA2：宫颈癌的一种新治疗策略。
Targeting HSP70-E7 Interaction With SHetA2: A Novel Therapeutic Strategy for Cervical Cancer.
机构信息
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Division of Molecular Diagnostics and Molecular Oncology, ICMR-National Institute of Cancer Prevention and Research, Noida, India.
出版信息
J Med Virol. 2024 Nov;96(11):e70088. doi: 10.1002/jmv.70088.
Cervical cancer is predominantly driven by persistent infections with high-risk human papillomavirus and the continuous activity of its E6 and E7 oncoproteins. This study explored the role of heat shock proteins 70 kDa (HSP70s) in enhancing the function of these oncoproteins and examined the impact of SHetA2, an investigational new drug, on this interaction. We found that HSP70 specifically binds to E7, but not E6, protein and that SHetA2 disrupts this binding. This disruption led to a significant reduction in E6 and E7 mRNA and E7 protein levels, while effects on E6 protein levels were minimal. SHetA2 treatment also resulted in altered levels of cell cycle regulatory proteins, reduced cell cycle progression, and decreased metabolic viability in cervical cancer cell lines and xenograft models. These findings support the potential of SHetA2 to impair cervical cancer progression by targeting HSP70/E7 interactions, highlighting its promise as a therapeutic strategy for treating cervical cancer.
宫颈癌主要是由高危型人乳头瘤病毒（HPV）的持续感染和其 E6 和 E7 癌蛋白的持续活性引起的。本研究探讨了热休克蛋白 70kDa（HSP70s）在增强这些癌蛋白功能中的作用，并研究了一种新型的实验性药物 SHetA2 对这种相互作用的影响。我们发现 HSP70 特异性地与 E7 蛋白结合，而不是 E6 蛋白，而 SHetA2 破坏了这种结合。这种破坏导致 E6 和 E7 mRNA 和 E7 蛋白水平显著降低，而对 E6 蛋白水平的影响则较小。SHetA2 处理还导致细胞周期调节蛋白水平发生改变，细胞周期进程减少，宫颈癌细胞系和异种移植模型的代谢活力降低。这些发现支持 SHetA2 通过靶向 HSP70/E7 相互作用来损害宫颈癌进展的潜力，突出了其作为治疗宫颈癌的治疗策略的前景。
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