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Effect Of Recombinant Super-compound Interferon (rSIFN-co) For Human Breast Cancer Cell

Posted on:2008-07-29Degree:MasterType:Thesis
Country:ChinaCandidate:J ZhengFull Text:PDF
GTID:2144360218960161Subject:Surgeon
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Objective:Breast cancer is one of the most common cancers of women, whose incidence rate now is much higher than it is before. As a systemic disease, breast cancer patients need not only regional treatment of operation, radiotherapy, but also systemic treatment of chemotherapy, endocrine therapy and immune therapy. The application of chemotherapy reduces the fatality rate of breast cancer a lot, but its severe side effect lowers the quality of patients' life. Besides more and more drug resistance decreases the therapeutic effect of chemotherapy. So it is important to find a way to enhance the anti-tumor effect, prolong life, but not to affect the life quality of breast cancer patient. Interferon (IFN) is a type of biologic-immune modulator, which has both anti-virus and anti-tumor effect. IFN can inhibit the tumor cell growth, obstruct the expression of oncogene, block the mitosis of the tumor cell, induce the cell differentiation and regulate the body immune system to kill tumor cell. It promotes the anti-tumor effect when chemotherapy combines with IFN. There are some studies reporting that IFN can reverse the drug resistance.The Recombinant Super-compound Interferon (rSIFN-co for short) is a new sequence of amino acids, which has all effective structures of IFN-α,β andω. After special purification, rSIFN-co gets a new protein conformation. This new conformation enable rSIFN-co has better anti-virus effect, and lower side effect. But the anti-tumor effect of rSIFN-co has been few reported. The objective is to investigate the anti breast tumor cell effect and the drug-resistance reversion effect of the rSIFN-co, and its cooperative anti-tumor effect with chemotherapy.Methods:1. Flow cytometry and MTT assays were used to determined the growth inhibition and cell apoptosis index (AI) of MCF-7 and MCF-7/ADR after different management of rSIFN-co, Infergen, Epirubicin.2. Immunohistochemical was used to detect the expression of P53,Bcl-2,CerbB-2,P-gp in MCF-7 and MCF-7/ADR after different management of rSIFN-co, Infergen, Epirubicin.Results:1. Cellular morphology: cell adherence in control group was symmetrical and the cells were in good condition. Cell adherence in intervention groups falls off obviously, and there was much more cell debris. This phenomenon was doses and time dependent.2. MTT: The optical density degraded significantly in every intervention group (P<0.05), and were doses and time dependent. rSIFN-co is better than Infergen.3. Flow cytometry: Low dose Epirubicin had little effect on the both tumor cells' apoptosis, compared with cell control group. But 5 jug/ml rSIFN-co, Infergen and rSIFN-co + Epirubicin and Infergen + Epirubicin resulted in much higher apoptosis (P<0.05). The rSIFN-co group and the rSIFN-co + Epirubicin group are more significant than Infergen and Infergen + Epirubicin group.4. Immunohistochemistry: The expression level of P53,Bcl-2,CerbB-2,P-gp of intervention groups had significant deviation compared with cell control group, after 48h incubation (P<0.05). The rSIFN-co group and the rSIFN-co + Epirubicin group are more significant than Infergen and Infergen + Epirubicin group.Conclusion:1. rSIFN-co can inhibit the growth of breast cancer cell MCF-7 and MCF-7/ADR.2. The inhibition of MCF-7 and MCF-7/ADR cell of rSIFN-co relates to the inducement of cell apoptosis.3. The inhibition of MCF-7 and MCF-7/ADR cell of rSIFN-co relates to lowering the expression of proliferation factors.4. The cooperative anti-tumor effect of rSIFN-co with Epirubicin on MCF-7/ADR cell relates to lowering the expression of P-glycoprotein, a multiple-drug resistance protein.
Keywords/Search Tags:rSIFN-co, breast cancer cell line, proliferation, apoptosis, drug resistance, flow cytometry, immunohistochemistry
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