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Antitumor Activity And Analysis Of Gene Expression Profiling Of Jinlongshe Granule In Human Gastric Caner Cell Line MKN-45

Posted on:2007-09-02Degree:MasterType:Thesis
Country:ChinaCandidate:Z H YuFull Text:PDF
GTID:2144360185957063Subject:Traditional Chinese Medicine
Abstract/Summary:PDF Full Text Request
OBJECTIVE: To assess the effects and decipher the mechanism of Jinlongshe Granules (JLSG) on tumor growth of gastric carcinoma, sarcoma 180 in vivo. METHODS: After establishment of the S180 model (subcutaneous tumor and ascites tumor), nude mice model orthotopic-transplanted with human gastric cancer cell lines MKN-45, the mice bearing-tumor were divided into 5 groups randomly: control group, 5-fluorouracil (5-FU)-treated (or CTX-treated) group and high-, medium-, and low-dose JSLG-treated groups. The antitumor effects in vivo were evaluated. Cell cycle distribution, apoptosis and ultrastructure of MKN-45 human gastric cancer cells were determined by using flow cytometry (FCM), Annexin V-FITC/PI staining assay and transmission electron microscope respectively. The cDNA genechip were used to further analyze the change of gene expression profiling in MKN-45 gastric cancer cell treated with JLSG. RESULTS: The inhibitory rates of JLSG at the three dose groups were 50.31%, 55.94% and 68.13% in nude mice models and 40.90%, 50.32% and 58.46% in S180 subcutaneous tumor, the rates of life prolongation for S180 ascites tumor were 38.46%,44.76% and 51.75%, and this antitumor effect was in a dose-dependent manner. The G0/G1 phase was arrested, the typical apoptotic peak appeared and compaction of nuclear chromatin and margination were observed in three JLSG-treated groups. An Annexin V-FITC/PI staining assay revealed that percentages of early apoptotic cells in the three dose JLSG-treated groups were all significantly higher than that in the 5-FU-treated group. 341 genes among the total 4096 (8.33%) showed expression difference in the cDNA chip assessments. CONCLUSION: JLSG exert an inhibiting effect on experimental tumor models in vivo by promoting the cell apoptosis, and its antitumor effect is multi-targeted. The TNF-related genes and bcl-2-related genes may involve in apoptosis-promoting action in MKN-45 human gastric cancer.
Keywords/Search Tags:Jinlongshe granules, stomach neoplasms, orthotopic transplantation, cell cycle, apoptosis, traditional Chinese medicine and pharmacy, nude mouse, Sarcoma 180, human gastric cancer cell line MKN-45, cDNA microarray
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