Tan Yuyong, Zhang Shilan, Zhu Hongyi, Chu Yi, Zhou Hejun, Liu Deliang, Huo Jirong
Department of Gastroenterology, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
Ann Transl Med. 2019 Jan;7(1):2. doi: 10.21037/atm.2018.11.48.
ACY1215 is a selective histone deacetylase 6 (HDAC6) inhibitor, and can suppress tumor growth for many human cancers. However, its role in colon cancer and its impact on the chemotherapeutic effect of 5-fluorouracil (5-Fu) are largely unknown. The aim of the present study is to explore the effect of ACY1215 on cell growth, migration, invasion and apoptosis, along with its impact on the chemotherapeutic effect of 5-Fu in HCT116 cells.
HCT116 cells were treated with ACY1215 with or without 5-Fu, and cell viability, proliferation, migration, invasion and apoptosis were explored.
The cell viability, colony formation number, wound closure rate, and migrated cell numbers of HCT116 cells significantly decreased, while the apoptotic cells significantly increased with the increased concentration of ACY1215 (P<0.05). The combination of ACY1215 and 5-Fu was more potent than either drug alone, as indicated by an increase of apoptotic cells, and by a decrease of cell viability, colony formation number, wound closure rate and migrated cell numbers. The expression of phosphorylated mitogen-activated protein kinases (pMEK) and phosphorylated extracellular-signal regulated protein kinase (pERK) were decreased when HCT116 cells were cultured with ACY1215.
Selective HDAC6 inhibitor, ACY1215, could inhibit the cell proliferation, migration and invasion, and induce apoptosis of HCT116 colon cancer cells. Furthermore, ACY1215 may enhance the chemotherapeutic effect of 5-Fu in HCT116 cells.
ACY1215是一种选择性组蛋白去乙酰化酶6（HDAC6）抑制剂，可抑制多种人类癌症的肿瘤生长。然而，其在结肠癌中的作用及其对5-氟尿嘧啶（5-Fu）化疗效果的影响尚不清楚。本研究旨在探讨ACY1215对HCT116细胞的细胞生长、迁移、侵袭和凋亡的影响，以及其对5-Fu化疗效果的影响。
用或不用5-Fu处理HCT116细胞，探讨细胞活力、增殖、迁移、侵袭和凋亡情况。
随着ACY1215浓度的增加，HCT116细胞的细胞活力、集落形成数、伤口闭合率和迁移细胞数显著降低，而凋亡细胞显著增加（P<0.05）。ACY1215与5-Fu联合使用比单独使用任何一种药物更有效，表现为凋亡细胞增加，细胞活力、集落形成数、伤口闭合率和迁移细胞数减少。当HCT116细胞与ACY1215一起培养时，磷酸化丝裂原活化蛋白激酶（pMEK）和磷酸化细胞外信号调节蛋白激酶（pERK）的表达降低。
选择性HDAC6抑制剂ACY1215可抑制HCT116结肠癌细胞的增殖、迁移和侵袭，并诱导其凋亡。此外，ACY1215可能增强5-Fu对HCT116细胞的化疗效果。
