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Effect Of Antitumor Drugs On Cell Cycle Of Human Gastric Cancer Cells

Posted on:2005-02-07Degree:DoctorType:Dissertation
Country:ChinaCandidate:M W HaFull Text:PDF
GTID:1104360122990980Subject:Oncology
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IntroductionCancer cells differ from normal cells in many important characteristics, including loss of differentiation, increased invasiveness, and decreased drug sensitivity. These differences do not arise simply from uncontrolled cellular growth but rather from a process of cellular evolution. Cell cycle plays an important role in the modulation of growth of tumor cells, and attention has been paid to preventing unlimited proliferation of tumor cells by cell cycle control. Completion of the cell cycle requires the coordination of a variety of macromolecular syntheses, assemblies, and movements. Coordination of the timing and order of these processes is achieved by a regulatory system which responds to checkpoints at major transitions in the cycle. Although our knowledge of cell cycle checkpoints is still incomplete, it is clear that many such control points exist within the cell cycle and that they play a major role in maintaining the integrity of the genome. At least two checkpoints detect DNA damage, one at the G - S transition and one at the G2 - M transition. In addition, there is mitotic checkpoint, altered expression of cyclins A, B, and CDC2, all potential targets of mitotic checkpoint controls, occurs in some cancers. Here, we investigated the effect of Atrillidi and the potent phospholipid/Ca2+- dependent kinase ( PKC) inhibitor Stauros-porine (ST) on cell cycle of human gastric cell MGC803 and SGC7901 and its possible mechanism.Garlic has been used for over three thousand years in traditional Chinese medicine and is widely used in preventing manifold diseases all over the world. Garlic is the bulb of onion genus lily family plant, allitridi is a compound extracted from the bulb of garlic. Allitridi is an important constituent of garlic oil mainly containing diallyl trisulfide (DATS) and diallyl disulfide (DADS). Allitridi show many anticancer biologic activities, such as inhibiting nitrate reduc-tase so as to prevent cancer; enhancing anticancer activity of macrophages; in-creasing sensitivity of anticancer drugs, and so on. However, a definitive mechanism of anticancer activities of allitridi has not been established.Protein kinase C (PKC) isoforms are serine/threonine kinases involved in signal transduction pathways that govern a wide range of physiological processes including differentiation, proliferation, gene expression, membrane transport and the organization of cytoskeletal and extracellular matrix proteins. PKC isoforms are often overexpressed in disease states such as cancer. The important role played in processes relevant to neoplastic transformation, carcinogenesis and tumor cell invasion renders PKC a potentially suitable target for anticancer therapy. Staurosporine, a microbial alkaloid (indolocarbazole produced by Strep-tomyces sp. ) ,has been shown to be a potent inhibitor of a wide range of protein kinases, including different serine/threonine and tyrosine protein kinases, which acts by competing with the ATP - binding region of the kinase catalytic domain. Staurosporine has been reported to exert various pharmacological actions involving protein kinase C both in vivo and in vitro, such as diminishing the thrombin enhanced procoagulant activity, reducing the carbachol - induced insulin secretion. PKC function is altered in some neoplasias, and this dysfunction has been related to uncontrolled proliferation.Part one Effects of allitridi on cell cycle arrest of human gastric cancer cellsObjective.- To study the effect of allitridi on cell cycle of human gastric cancer cells lines MGC803 and SGC7901 and its possible mechanism; to study the effect of allitridi on human gastric cancer cells lines MGC - 803 and SGC -7901 and that combination of allicin with antitumor drugs enhances cytotoxicity of antitumor (drugs to these cancer cells.METHODS: To evaluate the proliferation inhibition of the cells by means of trypan blue dye exclusion and morphosis shown of these cells through electron microscope; to analyze the change of cell cycle using flow cytometry and cell mi-tot...
Keywords/Search Tags:Allitridi, Staurosporine, Gastric cancer cells, Cell cycle, p21WAF1, p16INK4, Antitumor drug, Apoptosis
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