Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholangiocarcinoma cell lines
Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholangiocarcinoma cell lines
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DOI：
10.2152/jmi.58.106
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发表时间：
2011-02-01
影响因子：
0.7
通讯作者：
Shimada, Mitsuo
中科院分区：
文献类型：
--
作者：
Iwahashi, Shuichi;Ishibashi, Hiroki;Shimada, Mitsuo
背景资料：组蛋白去乙酰化酶（HDAC）通过表观遗传学调节与肿瘤发生相关，其抑制剂（HDACIs）可诱导肿瘤细胞分化和凋亡。我们在体外研究了丙戊酸（VPA，HDACI）与5-氟尿嘧啶（5-FU）联合治疗的疗效。方法：采用人胰腺癌细胞系SUIT-2和人胆管癌细胞系HuCCT 1。通过细胞增殖测定评价细胞活力。我们确定了VPA与5-FU联合使用对这些细胞系的抗癌作用。结果如下：胰腺癌（SUIT-2）：未观察到5-FU（1.0 μ M）的作用，但在2.5或5.0 μ M剂量下分别识别出17%和30%的增殖抑制作用。VPA（0.5 mM）仅微弱降低细胞活力。然而，在5-FU（1.0 μ M）与VPA（0.5 mM）的组合中，观察到19%的抑制作用。胆管癌（HuCCT 1）：5-FU（1.0 μ M）不抑制细胞活力，但5-FU（2.5 μ M）抑制23%。VPA（0.5 mM）不抑制细胞活力，而VPA（1.0 mM）微弱地降低了11%。5-FU（1.0 μ M）和VPA（0.5 mM）的组合显着降低细胞活力的30%。结论：VPA可增强5-FU对肿瘤细胞的抗肿瘤作用。因此，5-FU + VPA联合治疗可能是胰腺癌和胆管癌患者有希望的治疗选择。
Background : Histone deacetylase (HDAC) is well known to be associated with tumorigenesis through epigenetic regulation, and its inhibitors (HDACIs) induce differentiation and apoptosis of tumor cells. We examined the therapeutic effects of valproic acid (VPA, a HDACI) with a combination of 5-fluorouracil (5-FU) in vitro. Methods : A human pancreas cancer cell line (SUIT-2) and a cholangiocarcinoma cell line (HuCCT1) were used. Cell viabilities were evaluated by a cell proliferation assay. We determined the anticancer effects of VPA combined with 5-FU in these cell lines. Results : Pancreas cancer (SUIT-2) : No effect of 5-FU (1.0 mu M) was observed, but 17% and 30% of proliferation-inhibitory effects were recognized in a dose of 2.5 or 5.0 mu M, respectively. Cell viability was only weakly reduced by VPA (0.5 mM). However, in combination of 5-FU (1.0 mu M) with VPA (0.5 mM), 19% of inhibitory effect was observed. Cholangiocarcinoma (HuCCT1) : 5-FU (1.0 mu M) did not suppress the cell viability, but 5-FU (2.5 mu M) suppressed by 23%. VPA (0.5 mM) did not suppress the cell viability, while VPA (1.0 mM) weakly decreased it by 11%. Combination of 5-FU (1.0 mu M) and VPA (0.5 mM) markedly reduced the cell viability by 30%. Conclusion : VPA augmented the anti-tumor effects of 5-FU in cancer cell lines. Therefore, a combination therapy of 5-FU plus VPA may be a promising therapeutic option for patients with pancreas cancer and cholangiocarcinoma.