Effect of vasoactive intestinal peptide on gastric adenocarcinoma.
OBJECTIVE
Vasoactive intestinal peptide (VIP) is a gastrointestinal hormone in the secretin-VIP family. It has been reported that VIP affects some tumor growth, and there is a VIP autocrine regulation in some cancers. However, the effect of VIP on gastric adenocarcinoma is not clear yet. The aim of the present study was to investigate the effect of VIP on gastric adenocarcinoma, especially autocrine regulation of VIP on gastric adenocarcinoma.


METHODS
VIP mRNA and protein, and its receptor mRNA (VIPR(1) and VIPR(2)) were measured in 15 normal antrum mucosa, 20 gastric adenocarcinoma tissues, and the SGC7901 gastric adenocarcinoma cell line by using reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry, or radioimmunoassay methods. The effect of the VIP protein and its antagonist (D-p-Cl-Phe6, Leu17)-VIP on SGC7901 cell growth was detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) method. The expressions of c-myc mRNA and ornithine decarboxylase (ODC) mRNA in SGC7901 cells before and after the incubated VIP protein and/or its antagonist were also measured by RT-PCR method.


RESULTS
The VIP mRNA expression in gastric adenocarcinoma tissues was significantly higher than that in normal antrum mucosa (P < 0.01). The VIP-positive immunoreactivity cells existed in 40% of gastric adenocarcinoma tissues, but not in normal tissues (P < 0.01). The VIP-positive immunoreactivity nerve fibers were observed in normal tissues, but not in adenocarcinoma tissues (P < 0.01). The expression rate of VIPR(1) mRNA in adenocarcinoma tissues was significantly lower than that in normal tissues, but that of VIPR(2) mRNA in the two kinds of tissues were similar (P > 0.05). In addition, the expression quantity of VIPR(1) mRNA and VIPR(2) mRNA in adenocarcinoma tissues was significantly lower than that in normal tissues (P < 0.05). SGC7901 cells expressed not only VIP mRNA and the VIP protein, but also VIPR(1) and VIPR(2) mRNA. 10(6) SGC7901 cells secreted 13.15 +/- 8.54 pg VIP on average. VIP did not affect the proliferation of SGC7901 cells, but the antagonist stimulated the proliferation of SGC7901 cells from 10(-5) to 10(-8) mol/L concentration incubated for 24-96 h. VIP downregulated the expressions of c-myc and ODC mRNA, but its antagonist upregulated their expressions.


CONCLUSIONS
The expression of VIP mRNA upregulates, but the expressions of VIPR mRNA downregulates in gastric adenocarcinoma tissues. The gastric adenocarcinoma tissues contain endocrine cells to secrete VIP, which show malignant specialities. The VIP autocrine regulation exists in SGC7901 cells, and potentially inhibits the proliferation of the cells by downregulating the expressions of c-myc and ODC mRNA. It suggests that VIP may play an important role in the regulation of the growth of gastric cancer cells.
Li
Guo-Hua
GH
Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
Qian
Wei
W
Song
Geng-Qing
GQ
Hou
Xiao-Hua
XH
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009955:Ornithine Decarboxylase / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*
D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide; D009955:Ornithine Decarboxylase