Regulation Of Ursolic Acid On Proliferation And Apoptosis Of Gastric Cancer Cells Via STAT3Signaling Pathway

Background Gastric adenocarcinoma is one of the most common maligmanciesand the leading cause of cancer death in the world, especially in Eastern Asia.Althogh many studies have suggested infection by helicobacter pylori, diet, tobaccosmoking and hereditary factors are correlated with gastric cancer, little is knownabout its molecular process of development and progression still now.Ursolic acid isa ubiquitous molecule in the plant kingdom with specific anticancer effects that havebeen shown in vitro and in vivo, although UA can inhibit proliferation and induceapoptosis of many types of tumer cells, the molecular mechanism of its anti-canceractivity is still not well defined.Signal transducer and activator of transcription（STAT） proteins are kinds of important signal trancducers and transcription factorsthat mediate normal cellular responses to cytokines, growth factors, and otherpolypeptide ligands.Aim To investigate the effects of ursolic acid on cell proliferation and apoptosis incyclooxygenase-2（COX-2）-expressing （SGC-7901） and-non-expressing （MGC-803）gastric cancer cell lines and to reveal whether the signal transducer and activator oftranscription3（STAT3） signaling pathway mediates these effects.Methods SGC-7901and MGC-803cells were seeded in RPMI-1640mediumsupplemented with10%heat-inactivated fetal calf serum and routinely incubated for 24h. After treatment with ursolic acid at a final concentration of10,20,40and80μmol·L^-1for24,36and48h, the cell proliferation was determined using MTTcolorimetric assay. Hoechst staining was used to observe the morphologic changesof apoptotic cells. Apoptosis rates were detected by flow cytometric analysis. Theexpression of STAT3, phosphorylated STAT3（p-STAT3）, COX-2and procaspase-3was detected by Western blot analysis.Results Ursolic acid significantly inhibited SGC-7901and MGC-803cellproliferation in a dose-and time-dependent manner. Hoechst staining showed typicalapoptotic morphologic changes in both SGC-7901and MGC-803cells treated withursolic acid. The apoptosis rates in SGC-7901and MGC-803cells treated with10⁸0μmol·L^-1ursolic acid for24h were （4.7±0.4）%and （3.3±0.2）%,（6.4±0.5）%and （4.6±0.3）%,（9.9±1.8）%and （6.8±0.5）%,（14.5±1.7）%and （10.3±1.6）%,respectively. Ursolic acid dose-dependently inhibited STAT3phosphorylation in bothSGC-7901and MGC-803cells as well as COX-2expression in SGC-7901cells andprocaspase-3expression in MGC-803cells.Conclusions Ursolic acid inhibits proliferation and induces apoptosis of gastriccancer cells may be mediated by down-regulation of COX-2or procaspase-3expression through inhibition of the STAT3signaling pathway.