Dietary restriction suppresses tumor growth, reduces angiogenesis, and improves tumor microenvironment in human non-small-cell lung cancer xenografts
Dietary restriction suppresses tumor growth, reduces angiogenesis, and improves tumor microenvironment in human non-small-cell lung cancer xenografts
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DOI：
10.1016/j.lungcan.2012.11.001
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发表时间：
2013-02-01
期刊：
影响因子：
5.3
通讯作者：
Zhuang, Cong-Wen
中科院分区：
文献类型：
--
作者：
Lin, Bao-Quan;Zeng, Zhi-Yong;Zhuang, Cong-Wen
非小细胞肺癌（NSCLC）是全球癌症死亡的主要原因;然而，只有有限的治疗方法可用。本研究的目的是阐明饮食限制对人NSCLC异种移植瘤的治疗作用。向成年雌性裸小鼠的右背侧皮下注射NSCLC细胞系A549细胞。肿瘤植入后5天，动物被随机分为自由进食组（AL，平均每日摄入量的95%）或饮食限制进食组（DR，平均每日摄入量的70%）。植入后24天，发现DR抑制肿瘤生长，其标志为较低的肿瘤体积和重量。DR抑制肿瘤增殖，其标志是增殖细胞核抗原（PCNA）表达减少和活化的PCNA介导的凋亡。DR降低了微血管密度（以CD 31免疫染色减少为标志），促进了血管成熟（以α-平滑肌肌动蛋白（α-SMA）增加和因子VIII表达减少为标志）。DR降低瘤内间质液压力和衰减肿瘤缺氧检测EF 5免疫染色。此外，DR还能抑制NF κ B B信号通路，下调其下游蛋白环氧合酶2（考克斯-2）和诱导型一氧化氮合酶（iNOS）的表达。DR抑制磷脂酰肌醇3-激酶（PI 3 K）/AKT信号通路。总之，饮食限制抑制肿瘤生长，减少血管生成，并改善人类非小细胞肺癌异种移植瘤的肿瘤微环境。因此，饮食限制可以被设想为一种针对非小细胞肺癌的营养对策。(c)2012爱思唯尔爱尔兰有限公司保留所有权利。
Non-small-cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide; however, only limited therapeutic treatments are available. The aim of present study was to elucidate the therapeutic effect of dietary restriction in human NSCLC xenografts. Adult female nude mice were injected subcutaneously in the right dorsal flank with NSCLC cell line A549 cells. 5 days after tumor implantation, animals were randomly divided into ad libitum-fed group (AL, 95% of average diary intake) or dietary-restriction-fed group (DR, 70% average diary intake). 24 days after implantation, it was found that DR inhibited tumor growth marked by lower tumor volume and weight. DR suppressed tumor proliferation marked by reduced proliferating cell nuclear antigen (PCNA) expression and activated mitochondria-mediated apoptosis. DR decreased microvessel density marked by decreased CD31 immunostaining and promoted vessel maturation marked by increased alpha-smooth muscle actin (alpha-SMA) and reduced Factor VIII expression. DR reduced intratumoral interstitial fluid pressure and attenuated tumor hypoxia detected by EF5 immunostaining. In addition, DR suppressed NF kappa B signaling pathway and downregulation its downstream proteins expression including cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). DR suppressed phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. In conclusion, dietary restriction suppresses tumor growth, reduces angiogenesis, and improves tumor microenvironment in human non-small-cell lung cancer xenografts. Dietary restriction could thus be envisaged as a nutritional countermeasure against non-small-cell lung cancer. (c) 2012 Elsevier Ireland Ltd. All rights reserved.