Curcumin Promotes Apoptosis, Increases Chemosensitivity, and Inhibits Nuclear Factor κB in Esophageal Adenocarcinoma
Curcumin Promotes Apoptosis, Increases Chemosensitivity, and Inhibits Nuclear Factor κB in Esophageal Adenocarcinoma
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DOI：
10.1593/tlo.09235
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发表时间：
2010-04-01
影响因子：
5
通讯作者：
Chang, Andrew C.
中科院分区：
文献类型：
--
作者：
Hartojo, Wibisono;Silvers, Amy L.;Chang, Andrew C.
核转录因子kappaB是细胞存活和增殖的关键调节因子，它的激活可能导致肿瘤化疗耐药性的增强。姜黄素是一种口服的天然化合物，已被证明可以抑制核因子-kappaB，并在癌症化学预防中具有潜在的作用。我们观察了姜黄素对食管腺癌(EAC)中核因子-kappaB活性、细胞存活率以及与5-氟尿嘧啶(5-FU)或顺铂(CDDP)化疗增敏作用的影响。对46例Barrett化生、低度不典型增生、高度不典型增生和EAC的寡核苷酸芯片分析显示，与Barrett化生相比，EAC中NF-kappa B和I-kappa B激酶亚基的表达增加，效应因子caspase的表达降低。组织芯片分析检测到I-kappa B和磷酸化-I-kappa B在几个EAC组织中的基质表达。Western印迹分析、NF-kappa B报告基因分析和Caspase-Glo 3/7分析表明，姜黄素单独作用可抑制Flo-1和OE33 EAC细胞中的NF-kappa B活性并诱导其凋亡。它还能增加5-FU和CDDP诱导的两种细胞的凋亡。这些结果提示，核因子-kappaB的激活和细胞凋亡的抑制可能在Barrett化生向EAC发展过程中起作用。此外，众所周知的核因子-kappaB活性抑制剂姜黄素可促进细胞凋亡，增强5-FU和CDDP介导的化疗敏感性，提示姜黄素可能在EAC的治疗中有潜在的应用。
The transcription factor, nuclear factor kappa B (NF-kappa B), plays a central role as a key mediator of cell survival and proliferation, and its activation may confer increased tumor chemoresistance. Curcumin, an orally available naturally occurring compound, has been shown to inhibit NF-kappa B and has a potential role in cancer chemoprevention. We investigated the effects of curcumin on NF-kappa B activity, on cell viability, and as a chemosensitizing agent with 5-fluorouracil (5-FU) or cisplatin (CDDP) in esophageal adenocarcinoma (EAC). Oligonucleotide microarray analysis of 46 cases, consisting of Barrett metaplasia, low-grade dysplasia, high-grade dysplasia and EAC, showed increased expression of NF-kappa B and I kappa B kinase subunits and decreased effector caspase expression in EAC compared with Barrett metaplasia. Stromal expression of both I kappa B and phospho-I kappa B was detected in several EAC samples by tissue microarray analysis. Curcumin alone inhibited NF-kappa B activity and induced apoptosis in both Flo-1 and OE33 EAC cell lines as determined by Western blot analysis, NF-kappa B reporter assays, and Caspase-Glo 3/7 assays. It also increased 5-FU- and CDDP-induced apoptosis in both cell lines. These data suggest that activation of NF-kappa B and inhibition of apoptosis may play a role in the progression from Barrett metaplasia to EAC. In addition, curcumin, a well-known inhibitor of NF-kappa B activity, was shown to increase apoptosis and enhance both 5-FU- and CDDP-mediated chemosensitivity, suggesting that it may have potential application in the therapy of patients with EAC.