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Objective To explore the effect of psoralen on topoisomerase IIα(TopoIIα) expression of breast cancer stem cells.Methods CD44+CD24-/low breast cancer stem cells were sorted from MCF-7/ADR by magnetic-activated cell sorting(MACS).We observed the growth characteristics of these stem cells through optical microscope and detected the growth-inhibitory effects of psoralen on breast cancer stem cells by CCK-8 assay and IC50 of adriamycin and adriamycin combined with psoralen to calculate the reversal index.The mRNA and protein expressions of Topo IIα were detected using RT-PCR and Western blot, respectively.Results Under the optical microscope, breast cancer stem cells presented spheres.IC10 and IC20 of psoralen on breast cancer stem cells were (6.77±0.23)μg/mL and (10.36±0.21)μg/mL.IC50 of adriamycin and adriamycin combined with psoralen on breast cancer stem cells was (90.03±3.56)μg/mL and (21.47±0.82)μg/mL, the reversal index was 4.19.Psoralen significantly raised the expressions of Topo Ⅱα at mRNA and protein levels.Conclusion Psoralen reversed the resistance of adriamycin by increasing the gene and protein expressions of breast cancer stem cells Topo Ⅱα and the drug targets.
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Objective:To detect the expression and clinical significance of TOPO Ⅱ α 、Ki-67 and p53 in triple negative breast cancer (TNBC).Methods:The expression levels of TOPO Ⅱ α、Ki-67 and p53 were detected by IHC in 265 cases with invasive breast cancer.And analyze the relationship between the expressions and clinicopathoiogical features including tumor size,TNM stage,lymph node metastasis and histological grade.Results:Among 265 cases of breast cancer patients,TNBC patients accounted for 15.47％ (n=41),non-TNBC accounted for 84.53％ (n=224).the high expression rate of TOPO Ⅱ α,Ki-67 and p53 in TNBC were 78.05％,73.17％,and 65.85％,respectively,the difference was statistically significant compared with non-TNBC group (P＜0.05).The high expression of TOPO Ⅱ α was correlated with tumor volume,histological grading(P＜0.05);and the high expression of p53 was associated with histological grade,lymph node metastasis (P＜0.05);the high expression of Ki-67 was related with histological grade and tumor volume (P＜0.05).The expression of TOPO Ⅱ α,Ki-67 and p53 in TNBC was correlated.Conclusion:By detecting the expression of TOPO Ⅱ α,Ki-67 and p53,clinicians have a better understand of the biological behavior of TNBC,and provide an important basis for the selection of chemotherapy regimens.
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Objective To investigate whether Ki-67 and DNA topoisomerase Ⅱ α (Topo Ⅱ α) are effective prognostic markers in patients with primary hepatocellular carcinoma (HCC) after liver transplantation.Methods This retrospective cohort study included 105 patients with HCC who underwent liver transplantation in a single center from 2001 to 2012.The demographic features,clinicopathological data,expressions of Topo I c and Ki-67 as detected by immunohistochemistry.The long-term survival and the potential prognostic factors,together with standard histologic parameters,were analyzed by univariate and multivariate analyses.Results A positive correlation was found between Topo II α and Ki-67 levels in HCC (r ＝ 0.469,P ＜ 0.01).Multivariate analyses showed that Ki-67 was an independent prognostic risk factor of recurrencefree survival (HR ＝ 2.296,P ＜ 0.05).The 5-year overall survival rate was related to tumor size (HR ＝ 1.743,P ＜ 0.05),AFP (HR ＝ 2.291,P ＜ 0.05),histological grade (HR ＝ 0.283,P ＜ 0.01),and high expressions of Ki-67 (HR ＝ 1.977,P ＜ 0.05) and Topo Ⅱ α levels (HR ＝ 1.883,P ＜ 0.05).The KaplanMeier analysis showed that there was a significant difference in the 5-year recurrence-free survival rate (40.4％ vs.57.6％) between patients with high and low expressions of Ki-67,which were significantly lower in the high Topo Ⅱ α expression patients (13.5％ vs.63.8％) (P ＜0.01).The 5-year overall survival rates were significantly lower in the high Ki-67 expression patients (12.7％ vs.61.1％,P ＜0.01) when compared with the low Ki-67 expression patients,which were significantly lower in the high Topo Ⅱ α-and Ki-67 expression patients (10.7％ vs.54.5％,P ＜0.01) than the low Topo Ⅱ α-or Ki-67 patients.Conclusions Ki-67 was associated with recurrence and metastasis in patients with primary hepatic carcinoma after liver transplantation.High expression of both Ki-67 and Topo Ⅱ α were associated with poor prognosis in these patients.
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Aim To evaluate the antitumor activity of dianhydrogalactitol ( DAG) in vitro, and further clarify its underlying mechanisms. Methods The inhibitory effect of DAG in NCI-H460 cells was detected by CCK-8 assay and colony formation assay. The morphology of cells treated with DAG was observed under optical mi-croscope. Nuclear morphology was captured by fluores-cence microscopy after Hoechst 33342 staining. Real-time PCR was used to analyze the expression level of topoisomerase Ⅱ ( Topo Ⅱ) mRNA. The protein ex-pression level of Topo Ⅱ was detected by Western blot. Additionally, molecular docking approaches were used to predict the interaction between DAG and TopoⅡ. Results DAG exhibited potent antitumor activity in NCI-H460 cells, and inhibited cell proliferation per-sistently. DAG obviously induced nuclear morphologi-cal changes of NCI-H460 cells. Furthermore, DAG could down-regulate the mRNA and protein expression level of Topo Ⅱ detected by Real-time PCR analysis and Western blot, respectively. Molecular docking predicted that DAG could bind to Topo Ⅱ. Conclu-sion DAG can significantly inhibit the proliferation of NCI-H460 cells, and its underlying mechanisms may involve the down-regulation of Topo Ⅱ mRNA and di-rect binding to Topo Ⅱ, leading to cancer cell death.
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Objective To observe the expression of HER-2 and TOPO-Ⅱα in ovarian epithelial cancer,analyze the correlation between their expression and provide theoretical basis for clinical diagnosis,prognosis and treatment. Methods Expression levels of HER-2 and TOPO- Ⅱα in 10 normal ovarian tissues,20 benign tumors and 58 cases of ovarian epithelial cancers were detected by immunohistochemical method, and their correlations with pathological features were analyzed. Results The positive expression rate of HER-2 in normal ovarian and benign tumor tissues were significantly lower than ovarian epithelial cancers respectively ( 10. 0% , 15.0% VS 46. 6% ;P ＜ 0. 05 ). The positive expression rate of TOPO- Ⅱα in ovarian epithelial cancers was significantly higher than normal and benign epithelial ovarian tumor tissue (53.4% vs 10. 0%, and 15.0%,Ps ＜ 0. 05 ), but we did not find significant difference in the comparison between normal and benign epithelial ovarian tumor tissue ( Ps ＞ 0. 05 ). The expression of HER-2 and TOPO- Ⅱα were significantly correlated with clinical stages, histological differentiation of tumor cells (Ps ＜ 0. 05 ) ,but there were no correlations between the age or histological type. In ovarian cancer tissues, a positive correlation between the expression of HER-2 and TOPO- Ⅱα was observed ( r = 0. 324, P ＜ 0. 05 ) . Conclusion The overexpression of HER-2 and TOPO- Ⅱαplay an important role in ovarian carcinogenesis and development. The expression of HER-2 is positively correlated with TOPO- Ⅱα in ovarian epithelial cancers. Coexpression of the two moleculars may be involved in the development and progression of ovarian epithelial cancer, which should be further studied.
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Objective To detect the expression of HER2 and TOPOⅡ? in human breast cancer to explore the relationship between them and the potential value in the chemotherapy of breast cancer. Method 24 breast cancer tissues and paired normal tissues were investigated. RT-PCR and imumohistochemical staining were used to detect the expressions of HER2 and TOPOⅡ? at the transcription and protein level respectively. Results HER2 mRNA expressed positively in 29% (7/24) breast cancer tissues vs 4% (1/24) in paired normal tissues. The positive expression of TOPOⅡ? mRNA in breast cancer tissues and paired normal tissues were 92% (22/24) and 21%(5/24) respectively. The result of the immunohistochemical staining showed that the positive rates of HER2 and TOPOⅡ? in breast cancer tissues were 30%(6/20) and 94%(16/17) respectively, which was consistent with RT-PCR. The 6 cancer samples with HER2 positive expression coexpressed TOPOⅡ?. The expression of these two proteins was correlated(R=0.524,P
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Objectives To investigate the expression of hTERT, p16 and Topo-Ⅱ? in astrocytoma as well as their relationship during histogenesis and development of astrocytoma. Methods The expression of hTERT, p16 and Topo-Ⅱa in 64 astrocytoma specimens with different malignant grades and 10 normal brain tissues were studied using tissue microarray and immunohistochemistory. Results The expression rate of hTERT and Topo-Ⅱa were 50 % and 59.4 % respectively, they increased along with the increase of the malignant grade(P
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AIM: To observe the relationship between the reversal effect of 4 alkaloids of TCM on expression of P170 being obtained multi-drug resistance to mouse S180 tumor cell induced by chemotherapy protocol of PFC and the adjustment of the cell apoptosis.And to discuss the difference among alkaloids of TCM on reversion of being obtained multi-drug resistance in clinic.To improve the curative effect thereby. METHODS: By the methods of less dosage of Chemotherapy PFC,to set up the mouse models of multi-drug resistance of S180 tumor cell.At the same time to give the mouse matrine,terandrine,oxymatrine and berberine hydrooh loride for 2 weeks and then to observe the P170,TOPOⅡ,Fas and apoposis by flow cytometry. RESULTS: Matrine and terandrine could obviously reduce the expression of P170,the activation of TOPOⅡ induced by Chemotherapy and increase the ratio of the express of Fas and the apopsis of drug resistance to tumor cell.And berberine hydrochloride could obviously reduce the expression of TOPOⅡ. CONCLUSION: The adjustment to the apoposis of tumor cell by matrine and terandrine is related to the reversion of being obtained multi-drug resistance to tumor cell' expression,besides the different degree