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Objective:To study the role of adenoviral-mediated PTEN gene transfection in reversing drug resistance of trastuzumab-resistant human breast cancer.Methods:Recombinant adenoviruses carrying PTEN gene(AdPTEN) were constructed and transfected into trastuzumab-resistant human breast cancer cell line BT474.Proliferation and apoptosis of BT474 cells treated with AdPTEN and trastuzumab were measured by MTT assay and FCM.Time course of BT474 cells apoptosis induced by AdPTEN was analyzed by detection of DNA fragmentation.Western blotting was employed to measure phosphorylated-Akt expression levels in AdPTEN treated BT474 cells.The nude mice model of BT474 cells was employed to observe the effects of AdPTEN and trastuzumab on trastuzumab-resistant human breast cancer in vivo.The expression of PTEN gene,cancer cells apoptosis and ultrastructural changes were evaluated after the mice were sacrificed.Results:We successfully constructed recombinant AdPTEN;and the titer of the recombinant adenovirus was about 4.2?1011TCID50/ml.PTEN gene expression was identified by PCR,RT-PCR and Western blotting assay.Combinatorial AdPTEN and trastuzumab significantly suppressed the proliferation of BT474 cells and induced the apoptosis.The percentage of apopotosis cells treated with AdPTEN was(20.7?5.82)%,companied by cells cycle arrest in G1 phrase(P
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Biochemotherapy refers to the combination of biotherapy and chemotherapy,and it has been rapidly developed since its emergence.Biochemotherapy has brought both new therapies and new therapeutic ideas for the treatment of malignant tumors.In this article,we reviewed the recent advances in tumor biochemotherapies,including expansion of the indications,retaining of therapy even when tumor progressed(unique to biochemotherapy),and reversal of chemotherapy resistance by targeted therapy,the predicting response to tumor biochemotherapy,recent clinical trials of immunotherapy-based chemotherapy,and evaluation criteria for assessment of biochemotherapy response,and so on.
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Objective To explore the mechanism of the reversal of breast cancer resistant protein-mediated multidrug resistance by 17?-estradiol. Methods Two BCRP expressing cell lines of MCF-7/MX20 and MCF-7/BCRP were established in which breast canrcer resistant protein(BCRP) was promoted by BCRP promoter and cytomegalovirus(CMV) promoter respectively.These drug resistant cell lines were cultured in medium containing 17?-estradiol.Fourty-eight hours later,cytotoxicity assay,mitoxantrone efflux assays,quantitative RT-PCR were performed to observe the reversal function of BCRP by 17?-estradiol on MCF-7/MX20 and MCF-7/BCRP respectively. Results After being treated with 17?-estradiol,the intensity of mitoxantrone in MCF-7/BCRP was weaker than that in MCF-7/MX20 and the BCRP mRNA level in MCF-7/BCRP was high than that in MCF-7/MX20.The results of these experiments revealed that 17?-estradiol could reverse the BCRP mediated multidrug resistance(MDR) in MCF-7/MX20 cells but not in MCF-7/BCRP ones.Conclusion 17?-estradiol may reverse the phenotype of BCRP through regulation of the promoter of BCRP gene but not acted as the substrate of BCRP.