A novel role for 3, 4-dichloropropionanilide (DCPA) in the inhibition of prostate cancer cell migration, proliferation, and hypoxia-inducible factor 1alpha expression.

A novel role for 3, 4-dichloropropionanilide (DCPA) in the inhibition of prostate cancer cell migration, proliferation, and hypoxia-inducible factor 1alpha expression.
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DOI:
10.1186/1471-2407-6-204
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发表时间:
2006-08-02
期刊:
影响因子:
3.8
通讯作者:
Barnett JB
Barnett JB
中科院分区:
医学2区
文献类型:
--
作者:
Jiang BH;Liu LZ;Schafer R;Flynn DC;Barnett JB

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酰胺类化合物3,4-二氯丙酰苯胺(DCPA)可影响淋巴细胞和巨噬细胞的多种信号通路,包括抑制NF-κB的活性。然而,关于DCPA在癌细胞中的作用知之甚少。缺氧诱导因子1(HIF-1)调节许多基因的表达,包括血管内皮生长因子(VEGF)、血红素加氧酶1、诱导型一氧化氮合酶、醛缩酶、烯醇化酶和乳酸脱氢酶A。HIF-1表达与肿瘤发生和血管生成有关。用Transwell法检测细胞迁移,用免疫印迹法检测细胞内特异性蛋白表达。在这份报告中,我们证明,DCPA抑制DU 145和PC-3前列腺癌细胞诱导的血清,胰岛素,胰岛素样生长因子I(IGF-I)的迁移和增殖。我们发现DCPA以亚基特异性方式抑制血清和生长因子诱导的这些癌细胞系中HIF-1的表达,并通过影响其蛋白稳定性来降低HIF-1α的表达。DCPA可抑制前列腺癌细胞的迁移、增殖和HIF-1α的表达,提示DCPA有可能用于前列腺癌的治疗。
The amide class compound, 3, 4-dichloropropionanilide (DCPA) is known to affect multiple signaling pathways in lymphocyte and macrophage including the inhibition of NF-κB ability. However, little is known about the effect of DCPA in cancer cells. Hypoxia-inducible factor 1 (HIF-1) regulates the expression of many genes including vascular endothelial growth factor (VEGF), heme oxygenase 1, inducible nitric oxide synthase, aldolase, enolase, and lactate dehydrogenase A. HIF-1 expression is associated with tumorigenesis and angiogenesis. We used Transwell assay to study cell migration, and used immunoblotting to study specific protein expression in the cells. In this report, we demonstrate that DCPA inhibited the migration and proliferation of DU145 and PC-3 prostate cancer cells induced by serum, insulin, and insulin-like growth factor I (IGF-I). We found that DCPA inhibited HIF-1 expression in a subunit-specific manner in these cancer cell lines induced by serum and growth factors, and decreased HIF-1α expression by affecting its protein stability. DCPA can inhibit prostate cancer cell migration, proliferation, and HIF-1α expression, suggesting that DCPA could be potentially used for therapeutic purpose for prostate cancer in the future.
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