血管活性肠肽在体外和体内均可抑制人小细胞肺癌的增殖。
Vasoactive intestinal peptide inhibits human small-cell lung cancer proliferation in vitro and in vivo.
作者信息
Maruno K, Absood A, Said S I
机构信息
Department of Medicine, Northport Veterans Affairs Medical Center Stony Brook, NY 11768-2290, USA.
出版信息
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14373-8. doi: 10.1073/pnas.95.24.14373.
Abstract
Small-cell lung carcinoma (SCLC) is an aggressive, rapidly growing and metastasizing, and highly fatal neoplasm. We report that vasoactive intestinal peptide inhibits the proliferation of SCLC cells in culture and dramatically suppresses the growth of SCLC tumor-cell implants in athymic nude mice. In both cases, the inhibition was mediated apparently by a cAMP-dependent mechanism, because the inhibition was enhanced by the adenylate cyclase activator forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine in proportion to increases in intracellular cAMP levels, and the inhibition was abolished by selective inhibition of cAMP-dependent protein kinase. If confirmed in clinical trials, this antiproliferative action of vasoactive intestinal peptide may offer a new and promising means of suppressing SCLC in human subjects, without the toxic side effects of chemotherapeutic agents.
摘要
小细胞肺癌（SCLC）是一种侵袭性强、生长迅速且易转移、致死率高的肿瘤。我们报告称，血管活性肠肽可抑制培养的小细胞肺癌细胞的增殖，并显著抑制无胸腺裸鼠体内小细胞肺癌肿瘤细胞植入物的生长。在这两种情况下，这种抑制作用显然是由一种依赖环磷酸腺苷（cAMP）的机制介导的，因为腺苷酸环化酶激活剂福斯高林和磷酸二酯酶抑制剂3 - 异丁基 - 1 - 甲基黄嘌呤可根据细胞内cAMP水平的升高按比例增强这种抑制作用，而通过选择性抑制依赖cAMP的蛋白激酶可消除这种抑制作用。如果在临床试验中得到证实，血管活性肠肽的这种抗增殖作用可能为抑制人类小细胞肺癌提供一种新的、有前景的方法，且无化疗药物的毒副作用。
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