Department of Minimal Invasive Surgery, Ninbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China.
Drug Dev Res. 2021 Jun;82(4):598-604. doi: 10.1002/ddr.21780. Epub 2021 Jan 11.
As an anti-tumor agent, histone deacetylases (HDACs) inhibitors have attracted wide attention. ACY1215 is a highly effective selective inhibitor of HDAC6, which can inhibit many kinds of tumors. Whether the expression of HDAC6 and its new inhibitor ACY1215 can inhibit the proliferation of gallbladder cancer cells and induce their apoptosis remains to be further studied. The purpose of this study was to explore the effects of ACY1215 on the gallbladder cancer cells. Cell proliferation of GBC-SD and SGC-996 was assessed by cell counting kit-8 assay and colony formation assay. Flow cytometry was used to detect the apoptosis of gallbladder cancer cells. Western blot was used to detect the expressions of PCNA，KI67, and apoptosis-related proteins of gallbladder cancer cells. The HDAC6 inhibitor ACY1215 suppressed the proliferation of GBC-SD and SDC-996 cells and promoted the apoptosis of gallbladder cancer cells. The HDAC6 inhibitor ACY1215 increases the chemotherapy effect of gemcitabine and oxaliplatin. ACY1215 could suppress cell proliferation and induce apoptosis of GBC-SD and SGC-996, and increased the chemotherapy effect of gemcitabine and oxaliplatin, which provides a rationale for the combination of HDAC6 selective inhibitors with other anticancer agents in treating gallbladder cancer.
作为一种抗肿瘤药物，组蛋白去乙酰化酶（HDAC）抑制剂受到了广泛关注。ACY1215 是一种高效选择性 HDAC6 抑制剂，能够抑制多种肿瘤。HDAC6 的表达及其新型抑制剂 ACY1215 是否能够抑制胆囊癌细胞的增殖并诱导其凋亡仍需进一步研究。本研究旨在探讨 ACY1215 对胆囊癌细胞的作用。通过细胞计数试剂盒-8 检测和集落形成实验评估 GBC-SD 和 SGC-996 细胞的增殖。流式细胞术检测胆囊癌细胞的凋亡。Western blot 检测胆囊癌细胞中 PCNA、KI67 和凋亡相关蛋白的表达。HDAC6 抑制剂 ACY1215 抑制 GBC-SD 和 SDC-996 细胞的增殖并促进胆囊癌细胞的凋亡。HDAC6 抑制剂 ACY1215 增加了吉西他滨和奥沙利铂的化疗效果。ACY1215 能够抑制 GBC-SD 和 SGC-996 的细胞增殖并诱导其凋亡，并增加吉西他滨和奥沙利铂的化疗效果，为 HDAC6 选择性抑制剂与其他抗癌药物联合治疗胆囊癌提供了依据。
