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Experimental Study On Antitumor Effect Of Resveratrol

Posted on:2005-07-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:H LinFull Text:PDF
GTID:1104360125450065Subject:Physiology
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Resveratrol is a polyphenol found in different plant species and issynthesized by plants in response to pathogen attack. Resveratrol ispresent in high concentration in the skin of grapes and in wines butessentially nonexistent in white wine. Because of this, resveratrol hasbeen considered to be one of the candidate molecules to explain theFrench Paradox, a phenomenon that the French have relatively lowrates of ischemic heart diseases despite a large consumption ofsaturated fats and high serum cholesterol levels. Resveratrol displays numerous properties related to very differentmechanisms of action. Major activities of resveratrol include:modulation of lipid metabolism, inhibition of platelet aggregation,free-radical scavenging, anti-inflammatory activity, antitumor activity.Researches in antituomr effect of resveratrol are very popular in therecent years, but there is no systemic reports about its antitumoractivity in vivo and in vitro. At the same time, there are a variety ofviewpoints about its antitumor metabolism. To understand itsantitumor activity and to reveal its antitumor metabolism, we carriedout this experiment. In the first part of experiment, we studied in vivo the resveratrolon the inhibiting rate, increasing of life span, increasing effect anddecreasing toxicity while combined with cyclophosphamide andinfluencing lymphocyte transforming activity to mice. In the secondpart of experiment, we studied in vitro the resveratrol on the inhibitingeffect on the tumor cell lines of mouse and human. In the third part ofexperiment, we studied the apoptosis-promoting effect of resveratrolon K562 cells and observed the change of p21, caspase-3, p53 and bax.In the end, we observed the change of telomerase activity of K562cells. The results are as followed: 1. The in vivo inhibiting rate by high, middle and low doses ofresveratrol to H22 is 53.50%, 54.06% and 46.97%, respectively. Thein vivo inhibiting rate of high, middle and low doses of resveratrol toMFC is 64.37%, 49.73% and 50.24%, respectively. The in vivoinhibiting rate of high, middle and low doses of resveratrol to S180 is33.22%, 24.95% and 27.62%, respectively. 2. The increasing rate of life span by high, middle and low doses ofresveratrol to EAC-receiving mice models is 2.82%, 7.77% and15.47%, respectively. 3. Compared with the group which was only usedcyclophosphamide, the in vivo inhibiting rates of groups which werecombined with cyclophosphamide were no significantly increased butthe body weights of mice increased. 4. Compared with the control group, the lymphocyte transformingactivity of the mice spleen cells treated with resveratrol had no change. 5. The in vitro inhibiting rate by 100μg/ml, 30μg/ml, 10μg/ml, 3μg/ml and 1μg/ml doses of resveratrol to H22 cells is 99.67%,61.00%, 43.50%, 21.17% and 3.25%, respectively. The in vitroinhibiting rate by 100μg/ml, 30μg/ml, 10μg/ml, 3μg/ml and 1μg/ml doses of resveratrol to MFC cells is 100.00%, 71.50%, 50.00%,31.75% and 1.33%, respectively. The in vitro inhibiting rate by 100μg/ml, 30μg/ml, 10μg/ml, 3μg/ml and 1μg/ml doses ofresveratrol to K562 cells is 100.00%, 72.75%, 55.67%, 38.25% and10.00%, respectively. 6. Medial lethal dose of resveratrol (LD50) to H22, MFC and K562 invitro is 17.23μg/ml, 10.11μg/ml and 7.60μg/ml, respectively. 7. Treated with 10 μ g/ml of resveratrol, the ratio ofnucleus/cytoplasm of K562 cell decreases. Pycnosis and differentiationappears in nuclei. 8. DNA ladders appeared in the agarose gel in the tumor tissuetreated with resveratrol. 9. DNA ladders appeared in the agarose gel in K562 cells treatedwith resveratrol. 10. Levels of p21, caspase-3, p53 and bax mRNA transcriptionincreased in K562 cells treated with resveratrol. 11. Levels of P21 and Bax protein increased in K562 cells treatedwith resveratrol. 12. Colors of silver staining straps gradually f...
Keywords/Search Tags:Resveratrol, Tumor-inhibition in vivo, Lymphocyte transformation, Increasing of life span, Increasingeffect and decreasing toxicity, Tumor-inhibition in vitro, Apoptosis, p53, p21, bax, caspase-3, Telomerase
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