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The Effect Of Proliferation And Apoptosis Of Non-small Cell Lung Cancer A549 By Gemcitabine And Ginseng Polysaccharide In Vitro

Posted on:2007-10-14Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y WangFull Text:PDF
GTID:2144360242463446Subject:Respiratory medicine
Abstract/Summary:PDF Full Text Request
Background: Lung cancer is the leading cause of cancer-related death throughout the world,Lung cancer is primarily diagnosed during the advanced stage of disease,Approximately 30-40% of non-small cell lung cancer patients will present with metastatic disease,, at which stage treatment options are severely limited.Traditional treatments for metastatic non-small-cell lung cancer (NSCLC) include chemotherapy。During the 1990s, new cytotoxic agents such as irinotecan, paclitaxel, docetaxel, vinorelbine, gemcitabine, and amrubicin showed impressive single-agent activity in patients with lung cancer. Gemcitabine is one of the most active agents for the treatment of NSCLC. When combined with a platinum analog, gemcitabine produces the best progression-free survival outcome of any platinum-based regimen in first-line advanced NSCLC treatment setting。Gemcitabine-carboplatin is the most effective, convenient and cost effective. Polysaccharides are the major extracts of ginseng which is the one of Chinese traditional medicine .These extracts have been shown to enhance immune responses such as immunoglobulin production by lymphocytes and natural immune responses by peritoneal exudate macrophages. They have also been found to enhance anticomplementary and reticuloendothelial system activities, and induce messenger RNA expression of interleukin-2 (IL-2), interferon-gamma (IFN-γ), interleukin-1αand granulocyte-macrophage colony-stimulating factor as well as lymphokine-activated killer cells and CD8+ cells. In addition, these extracts appear to stimulate cell-mediated immune response and natural killer cell cytotoxicity as well as to have cytotoxic effects on a wide range of tumour cell lines without major histocompatibility complex restriction. TNF-related apoptosis inducing ligand(TRAIL) is a promising agent for development as a cancer therapeutic because it appears to specifically kill transformed and cancer cell,whereas most normal cells appear to be resistant to TRAIL.TRAIL induces apoptotic cell death upon binding to either of two pro-apototic TRAIL receptors, TRAIL R1(DR4) or TRAIL R2(KILLER/DR5 ).Bcl-2 is one of the most effective anti-apoptotic gene as we know,the expression is Bcl-2 protein,it can interdict the course of the Programmed cell death, then induce the occurring and development of the tumor.Objective: To observe the effect of proliferation and apoptosis of human non-small cell lung cancer treated by Gemcitabine and Ginseng polysaccharide in vitro, and the releationshilp between the expression of TRAIL and Bcl-2.Methods: The apoptosis of A549 induced by Gemcitabine and Ginseng polysaccharide were detected by MTT, Annexin-V—PI double-labeling, flow cytometry, and TUNEL approach. The changes of the expression of Bcl-2 and TRAIL after medicine treatment were examined by Western-blot.Results: The inhibitory action of cell growth was seen in A549 cell dealing with Gemcitabine and Ginseng polysaccharide. They could also promote the occurrence of apoptosis. Gemcitabine induce the S-phase arrest. The apoptosis induced by Gemcitabine was accompanied with the down-regulation of Bcl-2, the expression of TRAIL have not apparent change. Ginseng polysaccharide could induce the Go/G-phase arrest. The apoptosis induced by Ginseng polysaccharide was accompanied without the down-regulation of Bcl-2,but can found the up-regulation of TRAIL.Conclusion: Gemcitabine and Ginseng polysaccharide can synergistic inhibit the cell proliferation and induce the occurrence of apoptosis of A549 cell. The induced apoptosis, was one of the mechanisms of anti-tumor actions, which had certain relationship between the expression of Bcl-2 and TRAIL.
Keywords/Search Tags:Gemcitabine, Ginseng polysaccharide, apoptosis, human non-small cell lung cancer, Bcl-2, TRAIL
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