（N-硬脂酰，去甲亮氨酸17）血管活性肠肽杂合物抑制胰腺癌细胞系的生长。

(N-stearyl, norleucine17) VIP hybrid inhibits the growth of pancreatic cancer cell lines.

作者信息

Zia H, Leyton J, Casibang M, Hau V, Brenneman D, Fridkin M, Gozes I, Moody T W

机构信息

Cell and Cancer Biology Dept., Medicine Branch, National Cancer Institute, Rockville, MD 20850, USA.

出版信息

Life Sci. 2000;66(5):379-87. doi: 10.1016/s0024-3205(99)00604-9.

DOI:10.1016/s0024-3205(99)00604-9

PMID:10670826

Abstract

The effects vasoactive intestinal peptide (VIP) antagonists were investigated on pancreatic cancer cell lines. (N-Stearyl, Norleucine17) VIP hybrid ((SN)VIPhyb) inhibited 125I-VIP binding to human Capan-2 cells with an IC50 value of 0.01 microM whereas VIP hybrid had an IC50 value of 0.2 microM. By RT-PCR and Northern blot, VPAC1 receptor mRNA was detected in CAPAN-2 cells. One microM (SN)VIPhyb and 10 microM VIPhyb inhibited the ability of 30 nM VIP to elevate cyclic AMP and increase c-fos mRNA. (SN)VIPhyb, 1 microM inhibited the clonal growth of CAPAN-2 cells in vitro. In vivo, (SN)VIPhyb (10 microg/day s.c.) inhibited CAPAN-2 xenograft growth in nude mice. These results indicate that (SN)VIPhyb is a pancreatic cancer VPAC receptor antagonist.

摘要

研究了血管活性肠肽（VIP）拮抗剂对胰腺癌细胞系的作用。（N-硬脂酰基，去甲亮氨酸17）VIP杂合物（（SN）VIPhyb）抑制125I-VIP与人Capan-2细胞的结合，IC50值为0.01微摩尔，而VIP杂合物的IC50值为0.2微摩尔。通过RT-PCR和Northern印迹法，在CAPAN-2细胞中检测到VPAC1受体mRNA。1微摩尔（SN）VIPhyb和10微摩尔VIPhyb抑制30纳摩尔VIP升高环磷酸腺苷和增加c-fos mRNA的能力。1微摩尔（SN）VIPhyb在体外抑制CAPAN-2细胞的克隆生长。在体内，（SN）VIPhyb（10微克/天，皮下注射）抑制裸鼠中CAPAN-2异种移植瘤的生长。这些结果表明（SN）VIPhyb是一种胰腺癌VPAC受体拮抗剂。