| Gastric cancer is one of the most common malignant tumors. Approximately70thousand people annually died of gastric cancer all worldwide. The treatmentof gastric cancer mayor aim at tumor resection. However, surgical treatment only iswith high recurrence rates. Adjuvant treatment strategies have been studied in the lastdecades, but there have been many controversial results since the initialstudies.Therefore, scholars continue to search new approaches to the treatment ofgastric cancer.Signal transducer and activator of Transcription5A（STAT5A）is a member ofsignal transducer and activator of transcription,Immunohistochemical analysisdemonstrated differential expression patterns of the STAT5A is less in normal tissues,but increase in tumor tissues. In addition, STAT5A has a close relationship with tumorcell proliferation, differentiation, survival and apoptosis. In the downstream ofSTAT5A, there are many corresponding targets, and one of the important targets istelomerase. It has the effect on cell proliferation and differentiation. Therefore, thehigh proliferation of tumor cells maybe due to the increase of the expression ofSTAT5A,which inhiibits telomerase activity of cell proliferation.Trichostatin A (TSA) is a broad-spectrum histone deacetylase inhibitor, whichleads to differentiation, cell cycle arrest and apoptosis in tumor cells. It efficientlyprevent tumor growth in a variety of preclinical models in vivo. It is because TSA canregulate the histone acetylation level, which regulates tumor related gene transcriptionand the expression of protein, finally intervent tumor cells function.Many studies havereported that TSA can regulate the proliferation, apoptosis, cell cycle of gastric cancercells.However, the specific mechanism is still elusive. Objective:The purpose of experiments is to study whether TSA could impact the cellproliferation and cell cycle of gastric cancer cells by regulating the STAT5A; and toobserve whether it is related to the regulation of telomerase activity;to further explorewhether the intervention effect of TSA is regulated by class I HDACs activity.Method:To culture gastric cancer cell line SGC-7901,BGC-823and gastric epithelial cellline GES-1to detect the expression level of STAT5A by western blot. Determine thetime and dosage of TSA by CCK-8, and analysis the changes of STAT5A expressionafter treatment with TSA by western blot, Then observe the changes of both cellproliferation and cell cycle after treatment with TSA by CCK-8and flowcytometry.To detect the changes of telomerase activity after treatment with TSA byapplication of telomerase activity detection kit.To detect the changes of four HDACsactivity after treatment with TSA by HDACs activity kit.Results:The expression of STAT5A in gastric cancer cell line SGC-7901and BGC-823ishigher than gastric epithelial cell line GES-1, the comparison has significantdifferences (P <0.05). The expression of STAT5A in SGC-7901and BGC-823has reduced and which is time-dependent after300nM TSA treatment. Compared withSGC-7901the expression of STAT5A in BGC-823cells reduce more obvious aftertreatment with TSA. Treatment with300nM TSA for1-7days, the number of cells inSGC-7901and BGC-823was inhibited and cell cycle was arrested at G1phase; Inaddition, the telomerase activity of SGC-7901and BGC-823cell were reduced aftertreatment with TSA, especially BGC-823cell line,and the telomerase activity has asignificant difference (P <0.01); The activity of HDAC1,2,3,8in SGC-7901andBGC-823cells have vary degrees of decline, and the four kinds of HDACs inBGC-823activity decline is more apparent. Conclusion:1. The expression of STAT5A is higher in gastric cancer cell line SGC-7901andBGC-823; TSA could inhibit cell proliferation and arrest cell cycle in G1phase;2. TSA reduces the expression of STAT5A in a time-dependent manner,at thesame time reduces telomerase activity.3.TSA reduces the expression of STAT5A by reducing classⅠHDACs activity ingastric carcer cell. |
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