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Silencing MTA1 by RNAi Reverses Adhesion, Migration and Invasiveness of cervical cancer Cells (SiHa) via Altered Expression of p53, and E-cadherin/β-catenin Complex

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2011年第1期31卷 1-9页

作者：饶玉梅王鸿雁范良生陈刚 Department of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

It has been reported that metastasis-associated gene 1 （Mta1） is overexpressed in many malignant tumors with high metastatic potential. In addition, some studies indicated that MTA1 participated in invasion, metastasis, and survival of cancer cells by regulating cell migration, adhesion and proliferation. But the role of MTA1 is unclear in vitro in the development of cervical cancer cells. This study investigated whether and how MTA1 mediated cell proliferation, migration, invasion and adhesion in cervical cancer. MTA1 expression level was detected by Western blot in two cervical cancer cell lines of different invasion potentials. The effects of MTA1 expression on SiHa cell apoptosis, cycle, proliferation, migration, invasion and adhesion were tested by flow cytometry, MTT, wound-healing assay, Transwell assay and adhesion assay, respectively. The expression levels of p53, E-cadherin, and β-catenin activity were evaluated in untreated and treated cells. The results showed that MTA1 protein expression was significantly higher in SiHa than in HeLa, which was correlated well with the potential of migration and invasion in both cell lines. Furthermore, the cell invasion, migration and adhesion capabilities were decreased after inhibition of MTA1 expression mediated by Mta1-siRNA transfection in SiHa. However, no significant differences were found in cell apoptosis, cycle, and proliferation. In addition, E-cadherin and p53 protein levels were significantly up-regulated, while β-catenin was significantly down-regulated in SiHa transfected with the siRNA. These results demonstrated that MTA1 played an important role in the migration and invasion of cervical cancer cells. It was speculated that the decreased migration and invasion capability by inhibiting the MTA1 expression in the SiHa cell line may be mediated through the altered expression of p53, and E-cadherin/β-catenin complex. MTA1 could serve as a potential therapeutic target in cervical cancer.

关键词： metastasis-associated gene 1 RNA interference cervical cancer invasion migration

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MicroRNA-215 Is a Potential Prognostic Marker for cervical cancer

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2014年第2期34卷 207-212页

作者：梁华李艳洛若愚申复进 Department of Obstetrics and Gynecology Renmin Hospital of Wuhan University Department of Clinical Laboratory Renmin Hospital of Wuhan University

Recently, microRNAs （miRNAs） have been shown to be involved in multiple biological pathways that can influence tumor progression and metastasis and they can serve as prognostic bio- markers in many cancers. The present study examined the prognostic significance of miR-215 in cervi- cal cancer. The paraffin-embedded paired cervical scrape samples and tumor tissue samples from 302 patients with stage II cervical cancer were detected for the expression of miR-215 by using qRT-PCR. A miR-215-based classifier was established by using the Cox regression model. The prognostic and pre- dictive accuracy of this classifier was determined in both the internal testing group of 138 patients, and the external independent group of 280 patients. Moreover, cervical cancer HeLa cells overexpressing miR-215 （HeLa-miR-215） were constructed and subcutaneously injected into the nude mice to examine the effect of miR-215 on tumor growth and metastasis in vivo. The results showed that the expression level of miR-215 was significantly higher in cervical cancer tissues than in paired normal tissues （P〈0.0001）. When patients were classified into high- and low-risk cancer progression groups according to miR-215 level, the 5-year disease-free survival in high- and low-risk groups were 43% （95% CI： 32.1-51.6） and 67% （95% CI： 48.6-77.3）（hazard ratio [HR] 2.02, 95% CI： 1.16-3.52; P=0.013） re- spectively. Moreover, the expression level of miR-215 was negatively associated with survival rate in patients at TNM stage T3 （HR： 3.317; 95% CI： 1.18-5.14, P=0.017） and TNM stage T4 （HR： 3.48; 95% CI： 1.49-4.45, P=-0.008）. Tumor volume in nude mice injected with HeLa-miR-215 cells was signifi- cantly larger than that in mice injected with control HeLa cells. It was concluded that the expression level of miR-215 is associated with cervical tumor progression and worse survival rate, suggesting that it may serve as a potential prognostic marker to identify patients at higher risk of recurrence.

关键词： miR-215 microRNA cervical cancer prognosis

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Economic evaluation of cervical cancer screening strategies in urban China

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Chinese Journal of cancer Research 2019年第6期31卷 974-983页

作者： Li Ma Yuying Wang Xiaohong Gao Yi Dai Yu Zhang Zhaojing Wang Xiaoxia Wang Limin Wang Jing Jiang Xinhua Jing Chunxia Yang Fanghui Zhao Jinghe Lang Youlin Qiao Department of Epidemiology School of Public HealthDalian Medical UniversityDalian 116044China Department of Obstetrics and Gynecology Peking Union Medical College HospitalChinese Academy of Medical Sciences/Peking Union Medical CollegeBeijing 100730China Department of Obstetrics and Gynecology Wafangdian Maternal and Child Health Care HospitalDalian 116300China Department of Epidemiology and Biostatistics West China School of Public HealthSichuan UniversityChengdu 610041China Department of Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective:This study evaluated the feasibility of different cervical cancer screening strategies in urban China.Methods:A Markov model was constructed to simulate a hypothetical cohort of 100,000 females aged 30-59 years in a 20-year period.Screening strategies included liquid-based cytology(LBC)every three years,human papillomavirus(HPV)DNA testing every three and five years,respectively,and a combination of HPV DNA testing and LBC(HPV+LBC)every three and five years,respectively.Model outcomes included cumulative incidence over 20 years,cumulative risk of cervical cancer,costs,life year saved(LYS),quality-adjusted life years(QALYs)and benefits.The cost-effectiveness ratios(CERs),incremental cost-effectiveness ratios(ICERs),costutility ratios(CURs),and benefit-cost ratios(BCRs)were used as outcomes in the health economic evaluation analysis.Univariate sensitivity analyses were performed to examine the stability of the results.Results:The cumulative incidence of the five screening strategies ranged from 833.02 to 1,158.07 cases per100,000 females.HPV DNA testing was most effective in reducing the cumulative risk of cervical cancer,saving life years and QALYs and gaining benefits.The CERs of HPV DNA testing every three and five years,and LBC every three years were considered to be very cost-effective if they were below China's GDP per capita.The CERs of HPV+LBC were considered to be cost-effective if they were below three times GDP per capita.The incremental cost-effectiveness analysis showed that HPV DNA testing every three and five years,LBC every three years and HPV+LBC every five years were dominant strategies.Conclusions:The findings of this study indicated that HPV DNA testing every five years or LBC every three years should be recommended in urban China.

关键词： cervical cancer Markov model economic evaluation

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Realgar-Induced Apoptosis of cervical cancer Cell Line Siha via Cytochrome C Release and Caspase-3 and Caspase-9 Activation

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Chinese Journal of Integrative Medicine 2012年第5期18卷 359-365页

作者：程艳香刘嵘王琴李秉枢许学先胡敏陈璐付琼濮德敏洪莉 Department of Gynecology Renmin Hospital of Wuhan University Department of Obstetrics and Gynecology No.161 Air Force Hospital Department of Obstetrics and Gynecology Tongji HospitalMedical College of Wuhan University

Objective： To explore the molecular mechanism of realgar-induced apoptosis of cervical cancer cells. Methods： The cervical cancer cell line Siha was used to determine the cell viability and apoptosis after treatment with realgar using MTT assay and flow cytometry. The activities of caspase-3, -8, and -9 were detected by fluorescence resonance energy transfer technology and colorimetric assay, while the levels of Bcl-2, cytochrome c, and Bax were detected by Western blot method. Results： Induction of apoptosis by realgar was detected in Siha cell line in a dose-dependent manner. The apoptosis was accompanied by a significant increase in cytochrome c release and activation of caspase-3 and caspase-9 but not caspase-8. Further, the realgar-induced apoptosis was inhibited by a broad-spectrum caspase inhibitor, a caspase-3 inhibitor, and a caspase-9 inhibitor but not by a caspase-8 inhibitor. Bcl-2 and Bax protein expressions were not changed by realgar. Conclusion： The induction of apoptosis by realgar is mediated through a cytochrome c-dependent pathway, which sequentially activates caspase-9 and caspase-3.

关键词： realgar cervical cancer apoptosis cytochrome c caspases

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STAT3 Correlates with Stem Cell-related Transcription Factors in cervical cancer

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2015年第6期35卷 891-897页

作者：王华蔡红兵陈露露赵文君李盼王志强李蓁 Department of Gynecologic Oncology of Zhongnan Hospital of Wuhan University Hubei Cancer Clinical Study Center Hubei Key Laboratory of Tumor Biological Behaviors

Summary： cancer stem cells （CSCs） are considered responsible for the high recurrence rate in cervical carcinoma. It has been demonstrated that the signal transducer and activator of transcription 3 （STAT3） is involved in the oncogenesis and takes part in mediating the effects of maintaining stem cell phenotype and pluripotency by regulating the expression of stem cell-related transcription factors. However, the correlation between STAT3 and stem cell-related transcription factors in cervical cancer has not been elucidated. In this study, we established overexpressing plasmid （GV316-STAT3） and siRNA-STAT3 for transfecting Siha cells. Cells negative or positive for Nanog, Oct4, or Sox2 were selected by flow cytometry. Proliferation and differentiation rate of Siha cells was determined by detecting the efficiency of tumor sphere formation. The expression of Nanog, Oct4 and Sox2 （cancer stem cell markers） and STAT3 was detected by quantitative real-time PCR and immunoblotting for Siha cells and by immuno- histochemistry （IHC） for cervical tissues, respectively. The results showed that Nanog＋, Oct4＋, and Sox2＋ Siha-STAT3 over-expressing cells displayed the typical non-adherent spheres. The sphere for- mation efficiency was significantly different between Siha-STAT3 overexpressing cells and siRNA-STAT3 cells （P〈0.05）. Meanwhile, the expression levels of Oct4, Nanog and Sox2 rrtRNA and protein were significantly higher in Siha-STAT3 overexprssing cells than in siRNA-STAT3 cells （P〈0.05）. In addition, the positive rate of STAT3, Nanog, Oct4 and Sox2 in cervical cancer tissues was higher than that in chronic cervicitis group （P〈0.05）. There was a significantly positive relationship between STAT3 and Nanog or Oct4 or Sox2 expression （all P〈0.001）. These results suggested that Oct4＋, Sox2＋, and Nanog＋ cell population possesses stem cell properties in cervical cancer, which may contribute to cervical carcinogenesis and be regulated by STAT3.

关键词： signal transducer and activator of transcription 3 Nanog Oct4 Sox2 cancer stem cells cervical cancer

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Progress in the Study of Lymph Node Metastasis in Early-stage cervical cancer

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Current Medical Science 2018年第4期38卷 567-574页

作者： Bang-xing HUANG Fang FANG Dep-artment of Pathology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China Department of Gynecology and Obstetrics Renmin Hospital of Wuhan University Wuhan 430060 China

Spread into regional lymph node is the major route of metastasis in cervical cancer. Although lymph node status is not involved in the International Federation of Gynecology and Obstetrics staging system of uterine cervical cancer, the presence or absence of lymph node metastasis provides important information for prognosis and treatment. In this review, we have attempted to focus on the incidence and patterns of lymph node metastasis, and the issues surrounding surgical assessment of lymph nodes. In addition, the preoperative prediction of lymph node status, as well as the intraoperative assessment by sentinel nodes will be reviewed. Finally, lymph node micrometastasis also will be discussed.

关键词： lymph node metastasis cervical cancer sentinel lymph node micrometastasis

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Inhibitory Effect of HCPT on Expression of HIF-1α and Downstream Genes in Hypoxic Human cervical SiHa cancer Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2007年第5期27卷 586-589页

作者：施薇于世英 cancer Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

The hypoxic model to simulate hypoxic microenvironment in solid tumors was established and the effect of hydrocamptothecin （HCPT） on the hypoxia-induced over-expression of HIF-1α and VEGF genes was explored. Human cervical cancer SiHa cells were cultured in vitro under hypoxic conditions （37℃, 5% CO2, 1%O2） and treated with different concentrations of HCPT for 24 h. The mRNA and protein expression levels of HIF-1α, VEGF and Glutl in SiHa cells were detected by semi-quantitative RT-PCR and Western blot respectively. Normoxic control groups were exposed to normoxic conditions for 24 h. Under normoxic conditions, HCPT had no obvious effects on the HIF-1α and VEGF gene expression. Hypoxia induced the up-regulation of HIF-1α protein and downstream VEGF gene, and HCPT showed a dose-dependently inhibitory effect on the hypoxia-induced over-expression of HIF-1α protein and VEGF gene expression in SiHa cells, whereas HCPT had no significant effect on the HIF-1α mRNA expression. No difference in HCPT cytotoxic- ity was observed between hypoxic groups and normoxic control groups. It was suggested that HCPT could inhibite the expression of HIF-1α protein and downstream VEGF gene in hypoxic SiHa cells in a dose-dependent manner, and the inhibitory effect was not related with HCPT cytotoxicity.

关键词： hydrocamptothecin HIF-1α VEGF cervical cancer

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Inhibitory effect of lanthanum chloride on migration and invasion of cervical cancer cells

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Journal of Rare Earths 2013年第1期31卷 94-100页

作者：陈宏伟刘丝荪缪丽芳俞玲芳汪泱郭菲 Burns Institute The First Affiliated Hospital of Nanchang University Postgraduate Department of Nanchang University Department of Gynecology and Obstetrics The First Affiliated Hospital of Nanchang University Department of Gynecology and Obstetrics Jiujiang Maternal and Children Health Hospital

Tumor metastasis remains the main reason for treatment Jhilure and death of patients with cervical cancer. The prcsent study was designed to explore the effects of lanthanum chloride （LaCl3 on the invasion and migration of cervical cancel- cells and the underlying mechanisms. The migration and invasion of tumor cells was evaluated by a modified Transwell/Boyden chamber assays. It is well known that MMPs （Matrix metalloproteinases） and NF-κB （Nuclear factor-κB） pathway play important roles in migration and invasion of tumor cells, and also the expression of MMPs were regulated by NF-κB signaling. The expression on MMP-1 and MMP-9 was detected by reverse transcription polymerase chain reaction （RT-PCR）; Western blot and the NF-KB-DNA-binding ac tivity assay were used to analyze the NF-KB activity. The results indicated that LaCl3 was capable of inhibiting the cell invasion and migration of human cervical cancer Hela cells by decreasing the expression of MMP-1 and MMP-9 via blocking NF-κB pathway

关键词： lanthanum chloride （LaCl3） cervical cancer invasion migration： NF-~B rare earths

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HSP70 inhibitor combined with cisplatin suppresses the cervical cancer proliferation in vitro and transplanted tumor growth:An experimental study

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Asian Pacific Journal of Tropical Medicine 2017年第2期10卷 177-181页

作者： Jian Liu Jing Liu Su-Yang Guo Hong-Li Liu Sheng-Ze Li Gynecological Oncology the First Affiliated Hospital of Bengbu Medical CollegeBengbu City 233004Anhui ProvinceChina

Objective:To study the regulating effect of HSP70 inhibitor(PES) combined with cisplatin on cervical cancer proliferation in vitro and transplanted tumor growth.Methods:cervical cancer Hela cell lines were cultured and divided into control group,cisplatin group,PES group and cisplatin+PES group that were treated with serum-free DMEM,cisplatin with final concentration of 10 μmol/L,PES 20 μmol/L and cisplatin 10 μmol/L combined with PES with 20 μmol/L,respectively;animal models with cervical cancer xenografts were established and divided into control group,cisplatin group,PES group and cisplatin+PES group who received intra-tumor injection of normal saline,10 μmol/L cisplatin,20 μmol/L PES as well as 10 μmol/L cisplatin+20 μmol/L PES,respectively.Cell proliferation activity,transplanted tumor volume and mitochondria apoptosis molecule expression were detected.Results:Cell viability value and Bcl-2 mRNA expression in cells of cisplatin group,PES group and cisplatin+PES group were significantly lower than those of control group while Bax,Caspase-3 and Caspase-9 mRNA expression in cells were significantly higher than those of control group;transplanted tumor volume and the Bcl-2 mRNA expression in transplanted tumor tissue of cisplatin group,PES group and cisplatin+PES group were significantly lower than those of control group while Bax,Caspase-3 and Caspase-9 m RNA expression in transplanted tumor tissue were significantly higher than those of control group.Conclusions:HSP70 inhibitor combined with cislatin can inhibit cervical cancer cell proliferation in vitro and transplanted tumor growth through mitochondrial apoptosis pathway.

关键词： cervical cancer Heat shock protein 70 Transplanted tumor Mitochondrial apoptosis pathway

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Primary Screening for Breast Diseases among 17618 Women in Wufeng Area, a Region with High Incidence of cervical cancer in China

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2012年第2期32卷 252-256页

作者：张庆华刘眈黄传英胡婷沈健胡美玲杨茹陈枝岚来主会刘桂玲梅业冬向群英李雄黄科程王少帅潘秀玉严玉婷李夜陈茜奚玲邓东锐汪辉王世宣卢运萍马丁李双 Department of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Tech-nology Department of Obstetrics and Gynecology Wuhan Central Hospital Department of Maternity and Child Health Care Hospital Tujia Nationality Autonomous County

In this study, the current status for breast diseases in a region with high-incidence of cervical cancer were epidemiologically investigated. From March to August, 2009, 17618 women, from Wufeng area of Hubei province, China, were recruited to screen breast diseases by using breast infrared diagnostic apparatus. Other diagnostic methods, such as B-mode ultrasound, X-ray mammography, needle biopsy and pathological examination were, if necessary, used to further confirm the diagnosis. The screening showed that 5990 of 17618 cases (34.00%) had breast diseases, 5843 (33.16%) had mammary gland hyperplasia, 48 (0.27%) had breast fibroadenoma, 11 (0.06%) had breast carcinoma, and 88 (0.50%) had other breast diseases. The peak morbidity of breast cancer was found in the women aged 50–60 ages. The morbidity of breast cancer was significantly increased in women elder than or equal to 50 years old (n=8, 0.157%) in comparison with that in the subjects younger than 50 years old (n=3, 0.024%) (u=2.327, Pcervical cancer. Since the morbidity of breast diseases was higher among young women, more attention should be paid to the screening of breast diseases among young women for early diagnosis.

关键词： cervical cancer breast diseases screening high-incidence region

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