AB56. Down regulation of gastrin suppresses cell malignant proliferation in gastric cancer cell BGC823 through ERK and STAT3 activation

Abstract: The involvement of the gastrointestinal hormone gastrin in the development of gastric cancer is highly complex and deceptive, however, the exact cellular control mechanisms are still controversial. In this report, we validated the effects of over-expression of gastrin in gastric cancer and in gastric cancer cell lines to elucidate some of the mechanisms involving gastrin’s complex role in malignancy. In order to further clarify the influence of down-regulating gastrin on tumor biological characteristics and its molecular mechanisms, we constructed a gastrin specific short/small hairpin RNAs (shRNAs) interference vector and transfected it into the human gastric cancer cell line BGC823, and successfully obtained cell clones expressed by silenced gastrin. The knockdown of gastrin expression in BGC823 cells obviously decreases cell proliferation, reduces cell migration and invasion in vitro as assessed by MTT, soft agar colony formation assay, scratch assay, and transwell-assay. BALB/C nude mice that injected with gastrin shRNA transfected BGC823 cells showed significantly smaller tumor volumes than those in the control (non-gastrin inhibited) group. Finally, western blot analyses showed significant decreases in phosphorylation of ERK, STAT3 and in the expression of MMP11 in transfected cells. These results suggest that gastrin expression with MMP11 interference may occur via a pathway that includes stimulation of ERK and activation of STAT3 pathways, this putative mechanism may be the basis of the malignant proliferation of regulating gastric cancer cell, as well as its proclivity for invasion and migration.

Keywords: Gastric cancer; gastrin; molecular mechanisms; BGC823; ERK; STAT3; pathway