Aggarwal Bharat B, Shishodia Shishir, Sandur Santosh K, Pandey Manoj K, Sethi Gautam
Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Biochem Pharmacol. 2006 Nov 30;72(11):1605-21. doi: 10.1016/j.bcp.2006.06.029. Epub 2006 Aug 4.
Although inflammation has long been known as a localized protective reaction of tissue to irritation, injury, or infection, characterized by pain, redness, swelling, and sometimes loss of function, there has been a new realization about its role in a wide variety of diseases, including cancer. While acute inflammation is a part of the defense response, chronic inflammation can lead to cancer, diabetes, cardiovascular, pulmonary, and neurological diseases. Several pro-inflammatory gene products have been identified that mediate a critical role in suppression of apoptosis, proliferation, angiogenesis, invasion, and metastasis. Among these gene products are TNF and members of its superfamily, IL-1alpha, IL-1beta, IL-6, IL-8, IL-18, chemokines, MMP-9, VEGF, COX-2, and 5-LOX. The expression of all these genes are mainly regulated by the transcription factor NF-kappaB, which is constitutively active in most tumors and is induced by carcinogens (such as cigarette smoke), tumor promoters, carcinogenic viral proteins (HIV-tat, HIV-nef, HIV-vpr, KHSV, EBV-LMP1, HTLV1-tax, HPV, HCV, and HBV), chemotherapeutic agents, and gamma-irradiation. These observations imply that anti-inflammatory agents that suppress NF-kappaB or NF-kappaB-regulated products should have a potential in both the prevention and treatment of cancer. The current review describes in detail the critical link between inflammation and cancer.
尽管炎症长期以来被认为是组织对刺激、损伤或感染的局部保护性反应，其特征为疼痛、发红、肿胀，有时还伴有功能丧失，但人们对其在包括癌症在内的多种疾病中的作用有了新的认识。虽然急性炎症是防御反应的一部分，但慢性炎症可导致癌症、糖尿病、心血管疾病、肺部疾病和神经疾病。已鉴定出几种促炎基因产物，它们在抑制细胞凋亡、增殖、血管生成、侵袭和转移中起关键作用。这些基因产物包括肿瘤坏死因子（TNF）及其超家族成员、白细胞介素-1α（IL-1α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-18（IL-18）、趋化因子、基质金属蛋白酶-9（MMP-9）、血管内皮生长因子（VEGF）、环氧化酶-2（COX-2）和5-脂氧合酶（5-LOX）。所有这些基因的表达主要受转录因子核因子-κB（NF-κB）调控，NF-κB在大多数肿瘤中持续激活，并由致癌物（如香烟烟雾）、肿瘤启动子、致癌病毒蛋白（HIV-tat、HIV-nef、HIV-vpr、卡波西肉瘤相关疱疹病毒、EB病毒潜伏膜蛋白1、人嗜T淋巴细胞病毒1型税蛋白、人乳头瘤病毒、丙型肝炎病毒和乙型肝炎病毒）、化疗药物和γ射线诱导。这些观察结果表明，抑制NF-κB或NF-κB调控产物的抗炎药物在癌症的预防和治疗中可能具有潜力。本综述详细描述了炎症与癌症之间的关键联系。
