ABSTRACT
Objective To investigate the effects of chemotherapeutic drugs on ER-α expression and methylation in breast cancer cells.Methods Human breast cancer cells MCF-7(ER+,Luminal A) were induced by paclitaxel(PTX) and epirubicin(EPI) for more than 6 months,with an incremental dose,respectively.The expression and methylation status of ER-α in MCF-7 cells were detected before and after drug treatment.miRNAs with consistent expression changes in MCF-7 cells after two drugs' treatment were screened by microarray,and verified by quantitative PCR (qPCR).Targets of the most significantly down-regulated miRNA were analyzed by bioinformatics.miRNA inhibitor was transfected into MCF-7 cells,miRNA mimic was transfected into MCF-7/PTX and MCF-7/EPI cells,then ER-α and DNA methyltransferase 1 (DNMT1) expression were detected by Western blot,and ER-α methylation was detected by quantitative methylation-specific PCR (qMSP).Results PTX resistant MCF-7/PTX cell line and EPI resistant MCF-7/EPI cell line were established.Both drug treatments caused a decrease in ER-α protein expression and an increase in methylation levels,with up-regulation of DNMT1 and his tone deacetylase 1 (HDAC 1) expression.miRNAs with consistent expression changes in MCF-7 cells after drug treatments were screened and verified by qPCR,the most significant down-regulation among which was miR-148b.Bioinformatics analysis,and further confirmed by luciferase reporter gene assay (Luciferas) that DNMT1 was a direct target of miR-148b.miR-148b inhibitor induced decreased expression of ER-α and increased methylation level in MCF-7 cells,accompanied by increased expression of DNMT1;whereas miR-148b mimic caused an increased expression of ER-α and decreased methylation level in MCF-7/PTX and MCF-7/EPI cells,with a decreased expression of DNMT1.Conclusion Chemotherapeutic drugs (represented by PTX and EPI) induce aberrant miRNA expression in breast cancer MCF-7 cells,and down-regulate miR-148b further to attenuate the inhibition of DNMT1 expression,which promote,hypermethylation and down-regulation of ER-α.
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Objective:To explore the clinical effect of different surgical methods combined with Neoadjuvant chemotherapy in treating patients with breast cancer.Methods:80 patients treated and diagnosed in our hospital from January,2012 to January,2014 were enrolled in the present study.According to the willingness,physical condition and financial situation,they were divided them into group A (23 cases) and group B (57 cases).Neoadjuvant chemotherapy of EC regimens (epirubicin+cyclophosphamide) was applied to both groups,on the basis of which,group A received breast-conserving surgery,group B received modified radical mastectomy.The clinical effect,breast cosmetic result,life quality,psychological states were compared in both groups.Results:The operation time,extubation time were significantly shorter than those of group B (p ＜0.05),the amount of bleeding,AMA,HRSD score,occurrence rate of complications in group A were significantly lower than those of group B (p＜0.05),the breast cosmetic result of group A was obviously better than that of group B (p＜0.05),and the QLQ-BR23 score in group A was significantly higher than that of group B (p＜0.05).The 2-year survival rate and 2 year recurrence rate showed no statistical difference between the two groups (p ＞0.05).Conclusion:Breast-conserving surgery combined with epirubicin neoadjuvant chemotherapy was effective in treating breast cancer,which could decrease the complications,improve the breast cosmetic result and quality of life.
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Objective To explore Angptl2(angiopoietin-like protein 2)expression in tumor tis-sue and serum in patients with breast cancer(BC). Methods A total of 78 BC patients were enrolled in this study. Immunohistochemistry was used to detect Angptl2 expression in tumor and adjacent normal tis-sues. Preoperative and postoperative serum Angptl2 levels were determined via ELISA. Correlation among Angptl2 expression,clinicopathological factors and progression-free survival(PFS)were further evalua-ted. The receiver operating characteristics(ROC)curve was constructed to describe diagnostic specificity and sensitivity. Results Angptl2 was positively expressed in 64(82. 1% )cases. The rates of high and moderate expression of Angpt l2 in tumor and adjacent tissues were 53. 8%(42 / 78)and 7. 7%(6 / 78), respectively(P ﹤ 0. 001). Moreover,the elevated Angptl2 protein was significantly associated with lymph metastasis and adverse PFS. In addition,serum Angptl2 level in BC patients was significantly higher than that in benign controls[(218. 72 ± 88. 02)vs(80. 88 ± 30. 59)ng/ ml,P ﹤ 0. 01]. The area under the curve(AUC)was 0. 909,which indicated a good function for diagnosis. Postoperative serum Angptl2 level was decreased to(142. 43 ± 60. 29)ng/ ml,but still higher than that in controls(P ﹤ 0. 01). Conclusion The expression of Angptl2 may increase in tumor tissue and serum of BC and it may be a potential tumor marker for diagnosis and prognosis.