| At present, malignant tumor has become a major cause whichinfluences people's quality of life and threatens people's health severely. Sothe urgent affairs are to study the pathogenesis of tumor and developeffective anti-tumor drugs which can help the sufferers racked with cancerimprove their quality of life and prolong their life span. With thedevelopment of study, researchers recognize that apoptosis is a cellularvoluntary death controlled by gene and different from necrosis inmorphological and biochemical characters. Killing tumor cells by inducingapoptosis can protect the normal tissues of organism from intensiveinflammatory reaction. Therefore researchers pay more attention to the taskof developing drugs which can induce apoptosis of tumor cells.Gallic acidis a kind of Phenols compoud that is abstracted from plants,and it hasextensive biology effect. The present study was conducted to estimate theanti-cancer activity of GA in vitro and in vivo, and the mechanism ofaction.Purposes: To evaluate the antiproliferative activity of GA in vitro andin vivo and to elucidate potential mechanisms of action.Methods: The killing ability of GA on cancer cell was measured byMTT method;Tumor growth inhibition activity of GA was measured bymurine bearing in vivo;HT1080 cells were stained with Acridine orangeafter exposed with various concentrations of to do the morphologyexamination;Cell cycle was analyzed by flow cytometry;The expressionof bcl-2 and bax were analyzed by immunohistochemistry.Results:1.Murine Gastric cancer(MFC), Hepatoma(H22) and humanfibrosarcoma (HT1080) cell lines were treated with various concentrationsof GA for 48 hours. The results confirmed high anti-proliferation activityin all test cells, the IC50 values were 12.45,9.05 and 10.48μg/ml,respectively.2. The results of Gastric cancer(MFC) and Hepatoma-22(H22) tumorbearing mice tests approved that GA exhibited high experimentaltherapeutic activity on these two murine tumor models. In MFC models,the inhibition rates were 50.59%,41.65% and 30.27%, respectively, at thedose of GA 0.5, 0.25 and 0.2g/kg for 10-days consecutive administion;thetumor weight of 0.5, 0.25 and 0.2g/kg GA treatment groups weresignificantly(P<0.05) decreased to 1.02±0.32g,1.21±0.19g and 1.44±0.19g,while that of control group was 2.07±0.31g. In H22 models, theinhibition rate were 46.82%,40.41% and 31.99%, respectively, at the doseof GA 0.5, 0.25 and 0.2g/kg for 10-days consecutive administion;thetumor weight of 0.5, 0.25 and 0.2g/kg GA treatment groups weresignificantly(P<0.05) decreased to 1.23±0.21g,1.38±0.21 g and 1.51±0.24g, while that of control group was 2.31±0.25g.3. HT1080 cells were stained with Acridine orange after exposed withvarious concentrations of to do the morphology examination. The resultsshowed that, GA could induce cell nucleus condensed and few cellsundergoing apoptosis.4. Flow cytometery analysis results showed that 48-hour treatment ofGA trigged MFC cells undergoing apoptosis and caused G0/G1 arrest. Theapoptotic cell percentage(%) of control group was 11.10±1.13%, while thatof 25, 12.5 and 6.25μg/ml GA groups were 59.93±1.23%,49.03±1.36%and 48.15±1.45%, respectively. The percentage(%) of G0/G1 phrase were88.67±2.98%,85.88±2.74% and 84.19±4.51%, while the control groupwas 51.38±2.36%. Similar G0/G1 arrest induced by GA was seen in H22cells with obsolete variance. The percentage(%) of G0/G1 in control groupwas 56.55±4.15%, while that of 25, 12.5 and 6.25μg/ml GA groups were85.07±3.63%,78.63±2.32% and 77.66±2.68%, respectively.5. The result of immunohischemistry showed that GA restrained theexpression of bcl-2 on HT1080 after being treated with GA for 48 hours.The positive part reside cellular membrane, the control groups were stainedbrown, they were present powerful mascline, while that of 25, 12.5 and6.25μg/ml GA groups were present poor positive. Antibody bax's positivepart reside cellular membrane and cytoplasm, and the positive cells werebrown or dark brown. The control group cells were present poor mascline,while that of 25, 12.5 and 6.25μg/ml GA groups were present powerful ormidst positive. For this reason, GA facilitated the expression of bax protein,restrained the expression of bcl-2 on HT1080.1.GA exhibit high anti-proliferation activity in vitro.2.GA showed high experimental therapeutic activity on murine tumorbearing mice.3.GA exerted anti-proliferation proterty via causing G0/G1 arrest incancer cells.4.GA facilitated the expression of bax protein, restrained theexpression of bcl-2.In conclusion, GA could kill some cancer cells lines evidently. In thecase of GA induces apoptosis of cancer cells, it is maybe a principal agentthat GA evoke cell cycle hold up. Its causative factor is possible that freeradicals activate bax and down regulate bcl-2, and eventually cause cell totake place apoptosis. The discovery of GA's antitumor drug and scientificevidence for exploiting the traditional Chinese medicine.
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