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The Immune Effect Study Of The Lymphatic Targeting Anticancer Medicine Carbomycin

Posted on:2014-02-21Degree:MasterType:Thesis
Country:ChinaCandidate:J WangFull Text:PDF
GTID:2234330395498313Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Objective: To study the effects of activated carbon nanoparticles(ACNP)adsorbing MMC(ACNP-MMC) on the immune system and assess it’s applicationpotential in anti-tumor immune therapy.Method: Spleen cells of mice were isolated by aseptic method toprepare singlecell suspension.In vitro experiment, mouse spleen lymphocytes were exposed toMMC, ACNP and ACNP-MMC in final concentration of2.5,5,10,20,40,80μg/ml for48h.MTT assay and ELISA was respectively used to detect the proliferation and thesecretion of IL-2and IFN-γ induced by ConA in mouse spleen lymphocytes.Inorder to assess whether CBMC and MMC influnennce the immune system,H22livercancer mice model was used.CBMC and MMC were injected in mice inlow-dose(0.33mg/Kg), median-dose(1mg/kg) and high-dose(3mg/kg)respectitively.Macrophageic phagocytosis in mice was evaluated by utilizing the flow cytometryand detect the surface molecular markers of T lymphocyte by using flow cytometry.Results: The half inhibitory concentration (IC50) of MMC on mouse spleenlymphocytes was17.84μg/ml and that of ACNP-MMC was47.195μg/ml.Comparedwith normal control group, cell activity significantly decreased with rising of MMCconcentration. However, compared with MMC group, ACNP-MMC group was lessvenous for lymphocytes. ACNP can promote secretion of IFN-γ by mouse spleenlymphocytes. Compared with MMC group, the secretion of ACNP-MMC group wassignificantly increased(P<0.01). ACNP has no influence on the secretion of IL-2bymouse spleen lymphocytes. It has no significantly difference between ACNP groupand ConA group(P>0.05).However,Compared with MMC group, the secretion of CBMC group significantly increased(P<0.01). In the H22mice liver cancermodel,the percentage of phagocytic cells among low-dose, median-dose, high-dosegroups of CBMC were (28.99±0.52)%,(33.73±0.71)%,(29.14±0.16)%as well asthe phagocytic index were(0.497±0.003),(0.577±0.018),(0.449±0.013) respectively.Both significantly increased compared to control group[(25.34±0.21)%,(0.419±0.003)](P<0.05or P<0.01).Compared with MMC group, the proportion ofCD4+/CD8+andCD3+/CD19+in the low-dose of CBMC showed no significantdifference(P>0.05). However, the proportionality of CD4+/CD8+and CD3+/CD19+in the median-dose, high-dose groups of CBMC was higher than that in the MMCgroup(P<0.01), ACNP group and tumor saline group showed no significantdifference(P>0.05).Conclusion: CBMC can decrease the toxicity of MMC on mouse spleenlymphocytes and increase the secretion of IL-2and IFN-γ significantly.Promotes the phagocytosis of peritoneal macrophages, the activation level of immunecellular immunity effectively. CBMC has a higher potential at the aspect ofanti-tumor immune therapy.
Keywords/Search Tags:nanoparticles, mitomycin C, immune effect, spleen lymphocytes proliferation, IL-2, IFN-γ, macrophageic phagocytosis, surface molecular markers of Tlymphocyte
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