Inflammation and cancer prevention
Inflammation and cancer prevention
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DOI：
10.1093/annonc/mdn442
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发表时间：
2008-01-01
影响因子：
50.5
通讯作者：
Decensi, A.
中科院分区：
文献类型：
--
作者：
Puntoni, M.;Marra, D.;Decensi, A.
癌变是一个多年、多步骤、多途径的疾病进行性遗传和相关的组织损伤。化学预防-定义为使用药物或其他试剂来抑制、延迟或逆转这一过程-被认为是临床癌症研究中非常有前途和重要的领域[1，2]，并已被证明是降低乳腺癌、前列腺癌和结直肠癌（CRC）风险的有效策略[3-5]。一些流行病学[6]和实验[7]数据表明，炎症是肿瘤进展的重要因素，通过产生氧和氮自由基氧化剂、产生促生长细胞因子、抑制肿瘤抑制因子和刺激信号转导途径。一种在炎症过程中诱导的蛋白质，作为调节炎症和肿瘤基因的转录因子，促进蛋白可以证明是化学预防的关键分子靶点[8]。有证据表明NF-kB在癌症发生和癌症进展中起作用。炎症因子、致癌物、肿瘤促进剂和肿瘤微环境激活NF-κ B。NF-κ B和NF-κ B调节蛋白均与细胞转化、增殖、凋亡抑制、侵袭、血管生成和转移有关。此外，组成型激活的NF-kB发生在许多肿瘤中[8]。调节炎症分子靶点如环氧合酶（考克斯）[7]、诱导型一氧化氮合酶（NOS）[9]和脂氧合酶（LOX）[10]的药物已显示出有希望的化学预防活性。特别是，考克斯拮抗剂-包括阿司匹林、传统的非甾体抗炎药（NSAID）和考克斯-2选择性拮抗剂-在流行病学分析以及临床研究中显示出化学预防功效，并且正在观察到考克斯-2过表达或炎症的许多癌症靶点中进行评价。许多天然抗氧化剂（如绿色茶多酚、番茄红素、白藜芦醇、姜黄素和萝卜硫素）具有广谱抗炎和自由基捕获活性。这些药物在动物模型中显示出化学预防活性[11]，在人类研究中与较低的癌症风险相关[12]，似乎是开发的良好候选药物。
Carcinogenesis is a multiyear, multistep, multipath disease of progressive genetic and associated tissue damage. Chemoprevention—defined as the use of drugs or other agents to inhibit, delay or reverse this process—is recognized as a very promising and important area in clinical cancer research [1, 2] and has proved to be an effective strategy for risk reduction of breast, prostate and colorectal cancer (CRC)[3–5]. Several epidemiologic [6] and experimental [7] data implicate inflammation as an important factor in neoplastic progression via production of oxygen and nitrogen radical oxidants, production of growth-promoting cytokines, tumor suppressor inhibition and stimulation of signal transduction pathways.Nuclear factor-kB (NF-kB), a protein induced during inflammation that serves as a transcription factor regulating genes for inflammatory and tumor-promoting proteins could prove to be a key molecular target for chemoprevention [8]. Evidence suggests that NF-kB has a role in carcinogenesis and cancer progression. Inflammatory agents, carcinogens, tumor promoters and the tumor microenvironment activate NF-kB. Both NF-kB and NF-kB-regulated proteins have been linked to cellular transformation, proliferation, apoptosis suppression, invasion, angiogenesis and metastasis. Moreover, constitutively activated NF-kB occurs in many tumors [8]. Agents modulating molecular targets of inflammation such as cyclooxygenase (COX)[7], inducible nitric oxide synthase (NOS)[9] and lipoxygenase (LOX)[10], have shown promising chemopreventive activity. In particular, COX inhibitors—including aspirin, traditional non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 selective inhibitors—have shown chemopreventive efficacy in epidemiologic analyses as well as in clinical studies and are being evaluated in numerous cancer targets where COX-2 overexpression or inflammation is observed. Many natural antioxidants (eg green tea polyphenols, lycopene, resveratrol, curcumin and sulforaphane) have broad-spectrum anti-inflammatory and free radical trapping activities. These agents have shown chemopreventive activity in animal models [11], are associated with lower cancer risk in human studies [12] and seem to be good candidates for development.