A VASOACTIVE-INTESTINAL-PEPTIDE ANTAGONIST INHIBITS NONSMALL CELL LUNG-CANCER GROWTH

被引：143

作者：

MOODY, TW

ZIA, F

DRAOUI, M

BRENNEMAN, DE

FRIDKIN, M

DAVIDSON, A

GOZES, I

机构：

[1] NICHHD,DEV NEUROBIOL LAB,NEUROCHEM UNIT,BETHESDA,MD 20892

[2] WEIZMANN INST SCI,DEPT ORGAN CHEM,IL-78100 REHOVOT,ISRAEL

[3] TEL AVIV UNIV,SACKLER SCH MED,DEPT CHEM PATHOL,IL-69978 TEL AVIV,ISRAEL

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1993年 / 90卷 / 10期

关键词：

VASOACTIVE INTESTINAL PEPTIDE RECEPTORS; CAMP;

D O I：

10.1073/pnas.90.10.4345

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The most prevalent lung cancer, non-small cell lung cancer (NSCLC) has receptors for vasoactive intestinal peptide (VIP). Here the effects of a VIP antagonist (VIPhyb) on NSCLC growth were investigated. In vivo, when VIPhyb (10 mug, s.c.) was daily injected into nude mice, xenograft formation was significantly inhibited by almost-equal-to 80%. In vitro, VIP (100 nM) stimulated colony formation almost-equal-to 2-fold, whereas 1 muM VIPhyb inhibited colony formation by almost-equal-to 50% when adenocarcinoma cell line NCI-H838 was used. The attenuation of tumor proliferation is receptor mediated, as VIPhyb inhibited specific I-125-labeled VIP binding to cell lines NCI-H157 and NCI-H838 with an IC50 of 0.7 muM. VIP (10 nM) increased the cAMP levels 5-fold when cell line NCI-H838 was used, and 10 muM VIPhyb inhibited the increase in cAMP caused by VIP. Northern blot analysis and radioimmunoassays have shown VIP mRNA and VIP-like immunoreactivity in NSCLC cells. These data suggest that VIP may be a regulatory peptide in NSCLC and that VIPhyb is a VIP receptor antagonist that inhibits proliferation.

引用

页码：4345 / 4349

页数：5

共 48 条

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