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Cooperative Antitumor Effects Of Monkshood Polysaccharide Or RhIL-2 With Adriamycin Different Targeting Agents

Posted on:2005-08-02Degree:DoctorType:Dissertation
Country:ChinaCandidate:L F DongFull Text:PDF
GTID:1104360125458251Subject:Immunology
Abstract/Summary:PDF Full Text Request
Tumor is one of the main diseases that are threat to human health. Millions of people die from tumors every year. Although we have found different methods including surgery, radiation-therapy and chemotherapy to treat tumor disease, but the treatment effects are not perfect and also induces a multiplicity of side-effects. Therefore, it is necessary to find more efficient ways to control and cure tumors. One of the main methods is targeting therapy, but combining it with different therapeutic methods shows more potential. According to the Traditional Chinese Medicine Methodology, we use both "Fuzheng" and "Quxie" treatment methods combined on tumor. That means, while trying to eradicate the tumor cells, we should avoid injury the body immune function in-order to ensure the anti-tumor ability. Adriamycin is a chemotherapy drug that can eradicate many varieties of tumors when inserted into the tumor cell DNA molecule structure which inhibits the nucleic acid synthesizing. The key step in antitumor therapy is how to concentrate adriamycin only on tumor site while reducing the body side-effects. In this research, we use Monkshood Polysaccharide or rhIL-2 combined with different adriamycin targeting therapy agents to study the cooperative antitumor effects.Tumors cause decline in immune responses,which is detrimental to T cell and the NK cell functions。Tumors induce changes on the T cell proliferation, the cytokine production and expressions, the oncogenes expressions. In this study, we used tumor-bearing mice as the model, observed the antitumor effect (inhibitory rate), the life prolongation rate, the lymphocyte proliferation, the NK cells killing activity, the cytokine and oncogenes expressions, the activation-induced tumor cells apoptosis, the tissue pathology of different organs and so forth and so on, in-order to compare the antitumor effects of different treatment methods and understand their antitumor mechanism, to find more effective antitumor multipurpose methods. Objective: To investigate the antitumor effect of Monkshood polysaccharide (MPS) and acid Monkshood polysaccharide (AMPS) on mice transplanted with the tumor cell lines H22 and S180, explore their antitumor mechanism; To observe the cooperative inhibitory effects of Monkshood polysacchsride (MPS) or rhIL-2 with adriamycin magnetic albumin microspheres (ADM-MAM) or Adriamycin Liposome targeting therapy on established murine adenocarcinoma (H22) tumor, study the antitumor mechanism of multipurpose methods. Methods: (1) Drugs preparation: The MPS and AMPS were obtained from Monkshood by water extraction and alcohol precipitation. The mice with H22 and S180 tumor were given MPS or AMPS by oral peros (op) or by intraperitoneal injection (ip); The ADM-MAM was prepared by an improved method and was given to H22 tumor-bearing mice by tail vein injection; The adriamycin liposome (AL), adriamycin long circulating liposome (ALCL) and adriamycin long circulating temprerature-sensitive liposome (ALTSL) were prepared by reverse-phase evaporation method and were given to H22 tumor-bearing mice by tail vein injection. (2) Antitumor experiment: We used tumor-bearing mice as a modle: the antitumor activity was observed using the tumor weight as index, the life prolongation rate was observed according to the tumor-bearing mice survival days; (3) Pharmacokinetics determination: The tissue distribution of adriamycin in different categories of liposome was determined by HPLC method with in 24h after injection, the adriamycin concentration in heart and tumor were obseved. (4) Analysis on antitumor mechanism: The activity of natural killer (NK) cells and the lymphocyte transformation capacity were examined by the LDH and MTT methods respectively, the apoptosis of tumor cells and the expressions of p53, Fas, Fas-L and Caspase-3 were examined by flow cytometry (FCM), the expressions of splenic cell IL-2mRNA and IL-12mRNA were determined by RT-PCR, the tumor, heart, liver, kidney tissue pathology slices were made by HE coloration method. R...
Keywords/Search Tags:Monkshood polysacchsride, antitumor, adriamycin magnetic albumin microspheres, targeting therapy, rhIL-2, adriamycin long circulating temprerature-sensitive liposome, pharmacokinetics, anti-tumor mechanism
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