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@#To explore the mechanisms by which AKR1C3 induces tumor resistance, human breast cancer cell strain MCF-7/DOX resistant to doxorubicin, MCF-7/ AKR1C3 cells for overexpression of AKR1C3 and MCF-7/DOX-KD cells for knockdown of AKR1C3 in MCF-7/DOX cells were established. Western blot analysis found that AKR1C3 was expressed at a higher level in MCF-7/DOX than MCF-7 wild type cells. Similarly, CCK-8 and DAPI confirmed that MCF-7/ AKR1C3 cells were more resistant to DOX than AKR1C3 wild types as the IC50 was increased 6 times in MCF-7/AKR1C3 cells more than in AKR1C3 wild type cells. Meanwhile, colony formation ability was also enhanced after AKR1C3 was over-expressed in MCF-7 cells.Cytoplasmic/nuclear separation analysis and IF further found that β-catenin nuclear translocation mediated by AKR1C3 was the main reason contributing to the occurrence of DOX-resistant breast cancer cells. β-catenin inhibitor, XAV939, could reverse the AKR1C3 induced doxorubicin resistance in MCF-7 cells.Results indicated that AKR1C3 could be a potential therapeutic target in breast cancer cells.
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Objective To investigate the expression of Dickkopf-3 (DKK3) in human malignant melanoma cell lines and tissues,and to evaluate effects of DKK3 on the proliferation and apoptosis of malignant melanoma cell line A375.Methods Reverse transcription PCR (RT-PCR) and real-time fluorescence-based quantitative PCR (qRT-PCR) were performed to measure the mRNA expression of DKK3 in human malignant melanoma cell lines HM,A375,WM451,WM35,SK-MEL-1,Hs-695T and MDA-MB-435s,as well as in 38 primary melanoma tissues,4 metastatic melanoma tissues and 20 pigmented nevus tissues.Cultured malignant melanoma A375 cells were divided into 2 groups to be transfected with pcDNA3.1 (+)-Flag-DKK3 (experiment group) and pcDNA3.1 (+)-Flag-Vector (control group) respectively.The overexpression of DKK3 was verified by RT-PCR.Cell counting kit-8 (CCK8) assay and plate colony formation assay were performed to evaluate the proliferative activity of A375 cells,flow cytometry was conducted to detect apoptosis of A375 cells,and Western blot analysis was performed to determine the expression of cell cycle-and cell apoptosis-related proteins.Results The mRNA expression of DKK3 was downregulated in WM35 cells,absent in HM cells,A375 cells,WM451 cells,SK-MEL-1 cells and Hs-695T cells,but upregulated in MDA-MB-435s cells.Compared with pigmented nevus tissues,the mRNA expression of DKK3 was significantly decreased in malignant melanoma tissues (P ＜ 0.001).Compared with the control group (100％),cell colony formation was markedly suppressed in the experiment group (23.22％ ± 3.55％),and the proliferative activity of A375 cells was also significantly inhibited in the experiment group 24,48,72 hours after the transfection (all P ＜ 0.05).Flow cytometry showed that compared with the control group,A375 cells were significantly arrested in G1 phase (48.68％ ± 3.92％ vs.25.38％ + 2.92％,P ＜ 0.001),and the apoptosis rate of A375 cells was significantly increased in the experiment group (P ＜ 0.001).Compared with the control group,the experiment group showed significantly higher expression of p21,Bax,cleaved-parp and cleaved-casp3,but significantly lower expression of cyclin D1 and Bcl2 (all P ＜ 0.001).Conclusion DKK3 expression is downregulated in human malignant melanoma tissues,so it may serve as a potential tumor suppressor gene involved in the development of cutaneous malignant melanoma.
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Objective To investigate the effect of paroxetine in the adjuvant treatment of maintenance hemodialysis(MHD)com-plicating depression.Methods 60 patients with MHD complicating depression were randomly divided into the control group and the observation group,30 cases in each group.The control group received the routine therapeutical scheme(hemodialysis,complication treatment and correcting the renal anemia,etc).On the basis of the routine therapy the observation group was given oral paroxetine 10 mg/d,once daily for continuous 8 weeks.The depression level was assessed by the Hamilton depression scale(HAMD).The clinical symptoms,levels of Hb,ALB,Kt/V,iPTH,SF and HAMD scores were statistically analyzed and compared between the two groups.Results The clinical symptoms,levels of Hb,ALB,Kt/V after 8-week treatment in the two groups were significantly im-proved compared with pretherapy(P<0.05);the level of iPTH,SF and the HAMD scores in the two groups were decreased com-pared with pretherapy(P<0.05).The effective rate of depression was 86.67% in the observation group and 23.33% in the control group,the difference between the two groups had statistical significance(P<0.05).Conclusion Paroxetine in the assisted treat-ment of MHD complicating depression symptom can improve the quality of life in MHD patients.
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Objective To assess overall diagnostic value of SELDI-TOF-MS in early breast cancer. Methods To search and identify the relevent articals in English and Chinese from Jan. 1999 to Dec. 2007 on Medline,WeiPu full-text data base and Wan-Fang clara base, and the literatures have been integrated to review the quality rating, and the heterology examination and the meta analysis were conducted. While the summary receiver operating characteristic curve (SROC), pooled sensitivity, specificity and odds rate were calculated by SPSS13.0 software. Results 22 pertinent literatures can be indexed as a whole, of which 8 articles in-cluding 739 samples entered this Meta analysis. The pooled sensitivity, specificity and odds rate were 91.4% ,99.5% and 30.88 re-spectively. The area under the SROC curve was 0. 822 5. Conclusion SELDI-TOF-MS is valuable in diagnosis of ovarian cancer.