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Effects Of Lobaplatin On Apoptosis Of Human Gastric Cancer SGC-7901 Cells And Expressions Of AKT, PTEN And ERKmRNA.

Posted on:2012-08-07Degree:MasterType:Thesis
Country:ChinaCandidate:W J GaoFull Text:PDF
GTID:2214330338959032Subject:Internal Medicine
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Background and ObjectivesStomach cancer remained the fourth most common malignancy and the first common digestive maligant tumor and the second most frequent cause of cancer death in the world.Nearly 70% of new cases every year occurred in developing countries.It ranks first among all causes of death from cancer in China,with an annual mortality rate of approximately 25.2 per 100 000.The carcinogenesis and development of gastric carcinoma is multistage and a complicated process concerned of many ingredients.The main treatments for stomach cancer are surgery, chemotherapy, and radiation therapy.Stomach cancer found is adanced, surgery the effect not beautiful, must choose synthetic treatment.The significant side-effect of chemotherapy and drug resistance are also important reasons, the curative effect of chemotherapy needs improving.To explore the molecular mechanism of carcinogenesis and progression might improve its early detection, treatment and clinical outcome, and might also help to find new prognostic factors.With the development of molecular biology and cellular biology, the research progress of information channels, appeared targeted therapy and targeted drugs.Targeted drugs aimed at targets play antitumor function, can choose advantage crowd, avoid excessive treatment, so that patients were benefits.Cancer gene and tumor-suppressor gene were discovery, and ERK, AKT, PTEN, in cancer occurrence and development, in the role of the targeted therapy for cancer provide new targets, improve the therapeutic effect.Lobaplatin can inhibit the growth of SGC-7901 cells and induce apoptosis, the down-regulation of AKT and ERK mRNA and up-regulation of PTEN mRNA may be one of the mechanisms of the apoptosis.Observation AKT and ERK signaling pathways, key play in cell information transmission the key role.Materials and Methods1 Human SGC-7901 cells was chosen as the trial material.2 Chemotherapy drugs choose Lobaplatin.3 MTT assay was used to examine suppressive rate of cell growth dealt with different concentration and time of drugs, and the appropriate concentration of flow cytometry examination was determined.4 The development of cell cycle and apoptosis caused by different concentration management groups was examined by flow cytometry.5 To detect AKT, PTEN and ERK mRNA expression in SGC-7901 cells by RT-PCR assay.6 Analyzing the data with adopt normality inspection of SPSS 13.0, P<0.05 showed significant difference, P<0.01 says difference was very significant.Results1 MTT assay showed that different concentration and time of Lobaplatin could effectively inhibit the growth of cell line SGC-7901, compared all of the management groups, difference of OD value had statistical meaning (P<0.05),compared with all of the management groups to control group, the difference of OD value had statistical meaning (P<0.05).These results suggested Lobaplatin could significantly inhibit the growth and proliferation of SGC-7901 cells in vitro.Its degree was time-dose-dependent.2 According to the results of flow cytometry, different concentration and time groups of SGC-7901 cells dealt with Lobaplatin, the percents of apoptosis cells had statistical meaning (P<0.05).These results suggested Lobaplatin could arrest S phase cell and induce apoptosis. 3 Lobaplatin could inhibit the proliferation of SGC-7901 cells significantly.After acting with lobaplatin, the expression of the PTEN mRNA was significantly higher and the expression of the AKT and ERK mRNA was significantly lower.They were time and concentration dependent (P<0.05)Conclusions1 Lobaplatin could significantly inhabit the growth and proliferation SGC-7901 cells in vitro.They were time and concentration dependent.2 Lobaplatin tumor-suppressor role was correlated with the expression of Akt, ERK and PTEN mRNA in gastric cancer. After acting with lobaplatin, the expression of the PTEN mRNA was significantly higher and the expression of the AKT and ERK mRNA was significantly lower.3 Information pathways play a key role in proliferation and apoptosis.AKT is the key point in PI3K/Akt/mTOR signaling pathways.ERK is the key point in RAS/RAF/MEK/ERK signaling pathways.They played a critical role in cell information transmission.PTEN as tumor-suppressor gene may inhibit AKT and ERK gene expression, further indirect effect on the two messages pathways in tumorigenesis.4 Mechanism of the signaling pathways and the link between the pathways relations are not clear.So it still needs further study.
Keywords/Search Tags:Gastric tumor, Lobaplatin, flow cytometry, RT-PCR, MTT, AKT, PTEN, ERK
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