Ogasawara M, Murata J, Ayukawa K, Saimi I
Department of Pathogenic Biochemistry, Research Institute for Wakan-yaku, Toyama Medical and Pharmaceutical University, Japan.
Cancer Lett. 1997 Jun 3;116(1):111-6. doi: 10.1016/s0304-3835(97)00167-5.
We investigated the effect of neuropeptides, which are vasoactive intestinal polypeptide (VIP), substance P, (SP), neuropeptide Y (NPY), neurokinin A (NKA), somatostatin (SOM), calcitonin gene-related peptide (CGRP), and leucine-enkephalin (L-ENK), on the invasion of murine Colon 26-L5 adenocarcinoma cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. VIP, SP, NPY, and L-ENK reduced invasive potential of tumor cells in a concentration-dependent manner, whereas SOM, CGRP, and NKA had no effect. Especially, VIP showed the most effective in inhibiting tumor invasion, and achieved 50% reduction at 10(-6) M. A similar effect by VIP was also observed in cell migration to fibronectin. VIP had no effect on the growth of tumor cells at the concentrations ranging from 10(-10) to 10(-6) M. The suppressed ability of the tumor cell motility by VIP (10(-6) M) was practically recovered by co-treatment with 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor. These results indicate that VIP, among the neuropeptides used, could inhibit Matrigel invasion of Colon 26-L5 carcinoma cells through partial suppression of their motility, and the reduction was associated with an intracellular cAMP-mediated pathway.
我们使用Transwell细胞培养小室分析法，研究了神经肽（即血管活性肠肽（VIP）、P物质（SP）、神经肽Y（NPY）、神经激肽A（NKA）、生长抑素（SOM）、降钙素基因相关肽（CGRP）和亮氨酸脑啡肽（L-ENK））对小鼠结肠26-L5腺癌细胞通过重组基底膜（基质胶）侵袭的影响。VIP、SP、NPY和L-ENK以浓度依赖的方式降低了肿瘤细胞的侵袭潜能，而SOM、CGRP和NKA则没有影响。特别是，VIP在抑制肿瘤侵袭方面表现最为有效，在10^(-6) M时侵袭能力降低了50%。在细胞向纤连蛋白迁移方面也观察到了VIP的类似作用。在10^(-10)至10^(-6) M的浓度范围内，VIP对肿瘤细胞的生长没有影响。通过与腺苷酸环化酶抑制剂2',5'-二脱氧腺苷共同处理，实际上恢复了VIP（10^(-6) M）对肿瘤细胞运动能力的抑制作用。这些结果表明，在所使用的神经肽中，VIP可通过部分抑制结肠26-L5癌细胞的运动能力来抑制其对基质胶的侵袭，且这种降低与细胞内cAMP介导的途径有关。
