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Sensitivity To Chemotherapy Drugs Of Tumor Cell Line T47D With High SNCG Expression And SNCG Expression Analysis In Malignant Tumor Tissues

Posted on:2008-11-16Degree:MasterType:Thesis
Country:ChinaCandidate:B S HeFull Text:PDF
GTID:2144360215454211Subject:Cell biology
Abstract/Summary:PDF Full Text Request
Cancer is one of the major medical problems. The discovery of tumor-specific markers plays important role for the early diagnosis and clinical therapy. Recent studies have identified that breast cancer-specific gene 1 (BCSG1) andγ-synuclein (SNCG) was the same protein, which was closely correlated with breast and ovarian cancer. It is reported that SNCG is high-expressed in most advanced breast cancer and ovarian cancer, but the relationships between SNCG and other tumors was rarely reported. Therefore, our study was divided into two parts including experimental and clinical research to discuss the role of SNCG. In the part of experimental study, compared with human breast cancer cell line MCF-7, T47D cell line was used to observe the drug sensitivity to various chemotherapy drugs as DDP, ADM, 5-FU, VCR, TAX and CPT-11, and the effect of all types of chemotherapy drugs to the SNCG expression after treatment, exploring anti-cancer mechanism of various drugs. Clinical study analyzed SNCG expression in 160 cases of malignant tumor tissues and their para-cancer tissues by immunohistochemistry technique to discuss the expression characteristics and clinical significance to patients, providing evidence for the selection of individual chemotherapy.Experimental study results showed that the suppressing effects of all the chemotherapy drugs to T47D and MCF-7 cell lines were time-depended. Although there was no significant differences of effects of DDP, 5-FU after 60 hours between T47D and MCF-7 cell lines (P > 0.05), there were significant differences of the inhibiting roles of ADM, VCR, TAX and CPT-11 between MCF-7 and T47D cell lines. Compared with the controls, Proliferation index(PI) of T47D cell line decreased significantly when treated with DDP and 5-FU(P < 0.01), as well as ADM and CPT-11(P < 0.05) for 60 hours. The Caspase-3 expressions of T47D cell lines treated with the 6 drugs were all significantly higher than that of control (P < 0.01), moreover the Caspase-3 expressions of DDP and 5-FU were higher than other 4 drugs respectively (P < 0.01). After treated with DDP, 5-FU, ADM and CPT-11 for 60 hours, the expressions of SNCG of T47D cell were significantly lower than that of control (P < 0.01), but there was no difference between TAX, VCR treated group and control (P>0.05).Clinical results showed that there was significant difference of SNCG expression between tumor tissues and para-cancer tissue and normal tissue (P <0.01), and the positive rate and intensity of SNCG expression in malignant tumor tissues was positively correlated to the degree of differentiation (lower differentiation, higher SNCG expression), clinical stage (higher stage, higher SNCG expression) and tumor metastasis (with metastasis, higher SNCG expression).Conclusion:(1) T47D cell line with high SNCG expression was resistant to DNA enzymes antineoplastic agents (ADM, CPT-11) and anti-secession process of cell division, tumor-associated protein (VCR, TAX), while sensitive to drugs directly affecting DNA synthesis (DDP, 5-FU).(2) Both 5-FU and DDP may treat malignant tumor by inhibiting the SNCG expression, which can be used to investigate the anti-neoplasma mechanism(3) Detection of SNCG expression in malignant tumor tissues can be used not only in the auxiliary diagnosis of cancer, but also in the observation of disease progression and cancer patient prognosis, and it can provide the experimental basis for the selection of individual chemotherapy for cancer patients.
Keywords/Search Tags:γ-synuclein, Expression, T47D cell lines, Carcinoma, Individual chemotherapy
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