Expression Of Gastrin/Gastrin Receptor Loop In Many Tumors And The Effects Of Blocking The Loop On The Cell Proliferation And Apoptosis

Objective To study the expression levels of gastrin andcholecystokinin-B receptor (CCK-B) in a variety of tumors. The present study wasaimed at studying the effects of blocking the CCK-B receptor on cell proliferation andapoptosis in gastric cancer cells (SGC-7901, AGS), hepatocellular carcinoma cells(HepG2), lung cancer cells (A549) and breast cancer cells (MCF-7). A preliminarystudy on the signal pathway of the gastrin and CCK-B receptor loop. Method First,the expression of gastrin and CCK-B receptor protein in cancer tissue chips, clinicalspecimens of cancers (gastric,liver,lung,breast), and gastric cancer cells(SGC-7901,HepG2,A549,MCF-7)were measured by immunohistochemistry andimmunocytochemistry. Secondly,MTT was used to detect the cell proliferation and cellgrowth curve was drawn.The enzyme activity of Caspase-3in cells were detected byCaspase-3reagent box. Flow cytometry was used to measure the cell cycle, andAnnexin V-FITC/PI double staining was used to measure the apoptotic cells, andreal-time quantitative PCR was used to measure the expression of beta-catenin, nuelearfactor-P65(P65), phosphatidylinositol3-kinase(PI3K), mammalian target ofrapamycin(MTOR), and glycogen synthase kinase3beta(GSK-3β)mRNA of Wnt,NF-kb, PI3K-AKT-MTOR signal pathway in cells(SGC-7901, AGS) by proglumidetreatment. Results Gastrin was expressed in cancer tissue chips includingesophageal squamous cell carcinoma, gastric cancer, colon cancer, hepatocellularcarcinoma, lung squamous cell carcinoma, breast invasive ductal carcinoma, butnegative expressed in renal cell carcinoma. Gastrin and cholecystokinin-B receptor(CCK-B) were co-expressed in clinical specimens of cancers (gastric, liver, lung, breast)and gastric cancer cells (SGC-7901,AGS,HepG2,A549,MCF-7). Blocking the CCK-Breceptor by proglumide treatment inhibited the cell proliferation and increasedcaspase-3expression, and decreased the percentage of cells residing in the S-phase of the cell cycle, and increased the percentage of cells residing in the G1/G0-phase of thecell cycle, and meanwhile promoted cell apoptosis. Blocking the CCK-B receptor byproglumide treatment could down–regulate beta–caten and up-regulate PI3K mRNAexpression in SGC-7901and AGS cells, while the expression of P65, MTOR, GSK-3Bgene had no significant change. Conclusion Gastrin-CCK-B receptor autocrine loopwere presented in cancers (gastric, liver, lung, breast).Blocking the gastrin and CCK-Breceptor loop can inhibited the cell proliferation and promoted cell apoptosis in cancercells. Its mechanism may be related to gastrin-CCK-B receptor autocrine loopactivation of Wnt signaling pathway in the cells.