I-7ab 通过靶向 HDAC3 和促进 p53 乙酰化来抑制三阴性乳腺癌细胞的生长。
I-7ab inhibited the growth of TNBC cells via targeting HDAC3 and promoting the acetylation of p53.
机构信息
Department of Medical Oncology, Brunch of MinHang, Fudan University Shanghai Cancer Hospital, Shanghai, 200240, China.
Department of Medical Oncology, Fifth People's Hospital Affiliated to Fudan University, Shanghai, 200240, China.
出版信息
Biomed Pharmacother. 2018 Mar;99:220-226. doi: 10.1016/j.biopha.2018.01.063.
Triple negative breast cancer (TNBC) is a heterogenous disease with high aggressive and poor outcome. The lack of biomarkers and targeted therapies makes it a challenge for the treatment of TNBC. Histone deacetylase inhibitors (HDACis) are emerging as novel anti-tumor agents in many types of human cancers. In this study, we found that I-7ab, a novel HDACi, inhibited the cell viability of TNBC cells and induced the cell apoptosis. Mechanistically, I-7ab specifically decreased the expression of HDAC3 and promoted the acetylation of p53 at both Lys373 and Lys382 amino acids. The up-regulated acetylation of p53 promoted the transcriptional activity of p53 and induced the expression of p21, which consequently caused cell cycle arrest at G1 phase. Administration of I-7ab inhibited the colony formation of TNBC cells. Collectively, these results indicated I-7ab as a promising anti-cancer agent in the treatment of TNBC.
三阴性乳腺癌（TNBC）是一种具有高度侵袭性和预后不良的异质性疾病。缺乏生物标志物和靶向治疗药物使得 TNBC 的治疗成为一个挑战。组蛋白去乙酰化酶抑制剂（HDACi）在多种人类癌症中作为新型抗肿瘤药物崭露头角。在这项研究中，我们发现新型 HDACi I-7ab 抑制 TNBC 细胞的活力并诱导细胞凋亡。在机制上，I-7ab 特异性地下调 HDAC3 的表达，并促进 p53 在 Lys373 和 Lys382 氨基酸上的乙酰化。p53 的上调乙酰化促进了 p53 的转录活性，并诱导了 p21 的表达，从而导致细胞周期停滞在 G1 期。I-7ab 的给药抑制了 TNBC 细胞的集落形成。总之，这些结果表明 I-7ab 是治疗 TNBC 的一种有前途的抗癌药物。
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