Targeting NF-κB signaling pathway suppresses tumor growth, angiogenesis, and metastasis of human esophageal cancer
Targeting NF-κB signaling pathway suppresses tumor growth, angiogenesis, and metastasis of human esophageal cancer
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DOI：
10.1158/1535-7163.mct-09-0162
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发表时间：
2009-09-01
影响因子：
5.7
通讯作者：
Cheung, Annie L. M.
中科院分区：
文献类型：
--
作者：
Li, Bin;Li, Yuk Yin;Cheung, Annie L. M.
食管癌是第八大最常见的恶性肿瘤，也是全世界癌症相关死亡的主要原因之一。食管癌患者的总体5年生存率仍然很低，为10%至40%，这是由于晚期诊断、转移以及肿瘤对放疗和化疗的抵抗。NF-κ B B参与细胞生长、存活和运动的调节，但关于该信号通路在人食管鳞状细胞癌（ESCC）（食管癌的最常见形式）的肿瘤发生中的作用知之甚少。本研究旨在探讨NF-κ B B在食管鳞癌发生发展中的作用，并探讨靶向NF-κ B B信号通路对食管鳞癌的治疗价值。我们从人ESCC细胞系和ESCC组织的结果表明NF-κ B在ESCC中是组成性活性的。ESCC细胞暴露于两种NF-κ B抑制剂Bay 11 -7082和柳氮磺胺吡啶，不仅降低了癌细胞增殖，而且诱导了细胞凋亡并增强了对化疗药物5-氟尿嘧啶和顺铂的敏感性。此外，Bay 11 -7082和柳氮磺胺吡啶抑制ESCC细胞的迁移和侵袭潜力。更重要的是，肿瘤异种移植和实验转移模型的结果表明，Bay 11 -7082通过促进细胞凋亡、抑制增殖和血管生成，对裸鼠ESCC异种移植瘤具有显著的抗肿瘤作用，并减少ESCC细胞向肺部的转移，而无明显毒性作用。总之，我们的数据表明，NF-κ B B抑制剂可能是潜在的有用的治疗剂，食管癌患者。(Mol Cancer Ther 2009;8（9）：2635-44）
Esophageal cancer is the eighth most common malignancy, and one of the leading causes of cancer-related deaths worldwide. The overall 5-year survival rate of patients with esophageal cancer remains low at 10% to 40% due to late diagnosis, metastasis, and resistance of the tumor to radiotherapy and chemotherapy. NF-kappa B is involved in the regulation of cell growth, survival, and motility, but little is known about the role of this signaling pathway in the tumorigenesis of human esophageal squamous cell carcinoma (ESCC), the most common form of esophageal cancer. This study aims to explore the functions of NF-kappa B in human ESCC progression and to determine whether targeting the NF-kappa B signaling pathway might be of therapeutic value against ESCC. Our results from human ESCC cell lines and ESCC tissue indicated that NF-kappa B is constitutively active in ESCC. Exposure of ESCC cells to two NF-kappa B inhibitors, Bay11-7082 and sulfasalazine, not only reduced cancer cell proliferation, but also induced apoptosis and enhanced sensitivity to chemotherapeutic drugs, 5-fluorouracil, and cisplatin. In addition, Bay11-7082 and sulfasalazine suppressed the migration and invasive potential of ESCC cells. More importantly, the results from tumor xenograft and experimental metastasis models showed that Bay11-7082 had significant antitumor effects on ESCC xenografts in nude mice by promoting apoptosis, and inhibiting proliferation and angiogenesis, as well as reduced the metastasis of ESCC cells to the lungs without significant toxic effects. In summary, our data suggest that NF-kappa B inhibitors may be potentially useful as therapeutic agents for patients with esophageal cancer. (Mol Cancer Ther 2009;8(9):2635-44)