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The Prevention And Treatment Of Spinaon Gleditsiae On Lung Cancer And Its Mechanisms

Posted on:2015-02-08Degree:MasterType:Thesis
Country:ChinaCandidate:W J LiuFull Text:PDF
GTID:2284330431997326Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Lung cancer is one of the most malignant tumor, on human healthand life very serious threat.The incidence of malignancy has occupied thefirst place, and in the increased year by year, so the research on theprevention and treatment of lung cancer has important significance.Currently most lung cancer treatment using chemotherapy in thetreatment process is easy to produce toxic side effects and multi-drugresistance. However,Chinese medicine treatment of cancer with fewerside effects, can improve the patient’s quality of life and thecharacteristics of low cost of medicine won patients affirmation, andbecome an important source of development of new anticancer drugs, soscreening antineoplastic medicine became pharmacology researchhotspot.Total flavonoids from spinaon gleditsiae (TFSG) are pure extractsfrom Spinaon Gleditsiae,the previous study showed that the TFSG cansignificantly inhibit the proliferation of a variety of tumor cells. Thepurpose of this study was to observe the TFSG for prevention andtreatment of cancer, and to explore the possible new mechanism implied.In this study, MTT assay was used in vitro to detect the influence ofdifferent concentrations of TFSG on Mouse lung cancer cells (Lewis)(IC50=146μg/ml), mouse fibroblasts (L929), T lymphocyte proliferation, T lymphocyte effector cells,cell adhesion and gap junctional intercellualcommunication (GJIC) were measured through scrape loading and dyetransfer. In vivo experiments, Evaluation of TFSG for prevention andtreatment of cancer by Lewis subcutaneous allograft mouse model, Lewisexperimental lung metastasis mouse model and Urethane-induced lungcancer mouse model. Observation changes of mice in medical signs bydetecting the appearance, temperature, survival, self-activity of mousemodel; Impact assessment of TFSG on serum tumor-bearing mice bydetecting laminin (LN), platelet activating factor (PAF), tyrosine kinase B(TrkB), tyrosine kinase receptor (TrkA), mouse immunoglobulin G (IgG)levels change; Using scratches and dye observe GJIC andImmunohistochemistry observe the difference of TFSG lung tumor ofCx43to explore TFSG anti-cancer mechanisms.In vitro experiments showed that TFSG suppressed Lewis cellproliferation in a dose dependent matter but had no effect on L929cellproliferation in vitro. TFSG which has a little effect on cell proliferationdecreased cell attachment and promoted GJIC in a dose dependent matterin Lewis cells but didn’t affect L929cell attachment. At the same timecan increase the rate of lymphocyte proliferation and lethality oflymphocytes in mice.In vivo results showed that high dose and low dose of TFSG–treatedgroup can slow tumor growth rate prevent tumor metastasis and prolong survival time of tumor-bearing mice compare with Lewis subcutaneousallograft mouse model and Lewis experimental lung metastasis mousemodel with untreated. Urethane-induced mouse model of lung cancergroup had varying degrees of tumor nodules in mouse lungs, however,high dose and low dose of TFSG–treated group was able to preventcarcinogenesis induced by urethane. high dose and low dose ofTFSG–treated group can maintain a constant body temperature and goodliving conditions, reduce LN, PAF, TrkB, TrkA level, increase IgG levelsand improve the lung tissue pathology.Scratches and dye observe GJIC and Immunohistochemistry resultsshowed that TFSG which has a little effect on cell proliferation decreasedcell attachment and promoted GJIC in a dose dependent matter in Lewiscells and TFSG was able to enhance CX43staining in lung region withtumor in immunohistochemistry.In summary, TFSG have exact function of cancer prevention andtreatment, the mechanism is to increase immune function, enhancecommunication connections between cells, normalization of intercellularcommunication between cells, and thus can prevent tumor growth andmetastasis.
Keywords/Search Tags:total flavonoids from Spinaon Gleditsiae(TFSG), Gapjunctional intercellual communication (GJIC), lung cancer prevention, lung cancer treatment
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