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选择性抑制HDAC6对肾细胞癌具有抗癌作用的潜力。

Selective HDAC6 Inhibition Has the Potential for Anti-Cancer Effect in Renal Cell Carcinoma.

作者信息

Anraku Tsutomu, Murata Masaki, Kuroki Hiroo, Kazama Akira, Shirono Yuko, Tasaki Masayuki, Bilim Vladimir, Tomita Yoshihiko

机构信息

Department of Urology, Division of Molecular Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.

Department of Urology, Kameda Daiichi Hospital, Niigata 950-0165, Japan.

出版信息

J Pers Med. 2024 Jun 30;14(7):704. doi: 10.3390/jpm14070704.

Abstract

Despite significant advancements in systemic therapy for renal cell carcinoma (RCC), the prognosis for patients with metastatic RCC remains poor, as they are often incurable. Consequently, there is an urgent need for innovative therapeutic strategies to further enhance the efficacy of RCC treatment and improve patient outcomes. One such promising avenue lies in targeting histone deacetylase (HDAC) 6, a protein known to regulate numerous crucial biological processes implicated in cancer progression by modulating the acetylation status of various cytoplasmic proteins. To explore the therapeutic potential of HDAC6 inhibition in RCC, our study focused on investigating the effects of HDAC6 inhibitors on cultured RCC cells. Utilizing a panel of 12 small molecule selective HDAC6 inhibitors and employing genetic knockdown techniques, we examined the impact of HDAC6 inhibition on RCC cellular dynamics. Our findings revealed that HDAC6 inhibition exerted a profound effect on RCC cells, resulting in decreased cell viability and DNA replication. Importantly, this effect was attributed to the induction of apoptosis. Our study provides valuable insights into the mechanisms underlying the anticancer effects of selective HDAC6 inhibitors on RCC. A detailed understanding of the molecular mechanisms underlying the anticancer effects of HDAC6 inhibition is important to explore new therapeutic strategies for metastatic RCC.

摘要

尽管肾细胞癌(RCC)的全身治疗取得了显著进展,但转移性RCC患者的预后仍然很差,因为他们往往无法治愈。因此,迫切需要创新的治疗策略来进一步提高RCC治疗的疗效并改善患者预后。一个有前景的途径是靶向组蛋白去乙酰化酶(HDAC)6,该蛋白通过调节各种细胞质蛋白的乙酰化状态来调节许多与癌症进展相关的关键生物学过程。为了探索HDAC6抑制在RCC中的治疗潜力,我们的研究重点是研究HDAC6抑制剂对培养的RCC细胞的影响。我们使用一组12种小分子选择性HDAC6抑制剂并采用基因敲低技术,研究了HDAC6抑制对RCC细胞动力学的影响。我们的研究结果表明,HDAC6抑制对RCC细胞产生了深远影响,导致细胞活力和DNA复制下降。重要的是,这种作用归因于细胞凋亡的诱导。我们的研究为选择性HDAC6抑制剂对RCC的抗癌作用机制提供了有价值的见解。详细了解HDAC6抑制抗癌作用的分子机制对于探索转移性RCC的新治疗策略很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb36/11278056/3629e50c15c2/jpm-14-00704-g001.jpg

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