Publications (3)0.38 Total impact
Article: How does hypoxia inducible factor-1α participate in enhancing the glycolysis activity in cervical cancer?[show abstract] [hide abstract]
ABSTRACT: The objective of this study is to explore the role of hypoxia inducible factor-1 (HIF-1) in glycolysis activity and its relationship with malignant biologic behaviors of cervical cancer. Immunohistochemistry was performed to study the protein expression and distribution of HIF-1α and glucose transport protein 1 (GLUT1) in cervical tissue of 158 cases, including 28 with normal cervical epithelium, 32 with cervical intraepithelial neoplasia, and 98 with invasive cervical cancer. Cobalt(II) chloride was used to induce hypoxia in Hela and Siha cells; the biologic behaviors of cells cultured in normal or hypoxic environments were monitored by colorimetric, Transwell, flow cytometry, and enzyme-linked immunosorbent assay; immunocytochemistry, Western blot, and reverse transcription-polymerase chain reaction were used to observe gene and protein expression of HIF-1α, GLUT1, and hexokinase II in cell lines during normoxia and hypoxia. The expression of HIF-1α and GLUT1 gradually increased from normal cervical tissue to cervical intraepithelial neoplasia, then to cervical cancer. There were significant differences among these groups (P < .05). HIF-1α was strongly associated with pathologic differentiation, clinic stage, magnitude of lesions, and patient age, whereas GLUT1 was associated with lymphatic metastasis (P < .05). HIF-1α was strongly associated with expression of GLUT1 (P < .05). In hypoxia, proliferation, invasion, resistance to apoptosis, and glycolysis of both Hela and Siha were enhanced compared with cells in normoxia (P < .05). Both gene and protein expressions of GLUT1 and hexokinase II were strengthened, whereas only the protein expression of HIF-1α was stronger in hypoxia than that in normoxia (P < .05). The results of Hela in normoxia and in hypoxia were similar to those of Siha (P > .05). HIF-1α plays a key role in cervical cancer both in vivo and in vitro. The role of HIF-1α can be implemented mainly by up-regulating its downstream gene, such as GLUT1, and the main mechanism may enhance glycolytic ability. Strong up-regulation and the role of HIF-1α suggest that HIF-1α could be an important factor in the onset and progression of cervical cancer and could be an attractive therapeutic molecular target for that type of cancer.Annals of diagnostic pathology 01/2013;
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ABSTRACT: ObjectiveThe aim of our study was to observe the anti-tumor effect of silencing the expression of HIF-1α on cervical cancer in nude mice and to explore its mechanism of action. MethodsHuman cervical cancer cell line Siha cells were divided into 3 groups: mock control group, control group transfected with scrambled sequence plasmid, and experimental group transfected with pU-HIF-1a-shRNA eukaryotic expression plasmid. Cultured cells of the three groups were inoculated in nude mice to establish cervical cancer-bearing nude mice. HIF-1α RNAi assay was performed to evaluate the tumor-suppressive effect of HIF-1α silencing on cervical cancer-bearing nude mice. Immunohistochemistry and Western blot were used to observe the distribution and protein expression of HIF-1α and GLUT1, while RT-PCR was adopted to detect the gene expression of HIF-1α, GLUTl and HK II. The product of glycolysis (lactic acid) and apoptosis in tumor cells were detected by colorimetry and semi-quantitative TUNEL staining, respectively. ResultsThe tumor growth in experimental group was significantly slower than that in the two control groups (P < 0.05). In the 50th day after transplantation, the tumor weight in the experimental group was (1.90 ± 0.28) g, significantly lower than (2.95 ± 0.77) g in the control group and (2.54 ± 0.56) g in the mock group (P < 0.01). In the experimental group, the gene and protein levels of HIF-1α were 0.45 ± 0.04 and 1.25 ± 0.92, and the levels of GLUT1 were 0.32 ± 0.02 and 1.25 ± 0.48, respectively. Both indicators in HIF-1α and GLUT1 were lower than that in the two control groups (P < 0.05). The expression levels of HK II gene and lactic acid in the experimental group were lower than that in the two control groups (P < 0.05), but the apoptotic cells were much more numerous in the experimental group than that in matched control groups (P < 0.01). ConclusionThe gene therapy by siRNA targeted silencing of HIF-1α may down-regulate its downstream genes GLUT1 and HK II expression, therefore, to reduce the tumor glycolysis activity and promote tumor cell apoptosis, and exert a tumor-suppressing effect in vivo. Key wordscervical neoplasms-HIF-1α-GLUTl-RNAi technique-nude miceThe Chinese-German Journal of Clinical Oncology 04/2012; 9(7):416-421.
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ABSTRACT: This study investigated the anti-HSV-2 effect of alumen through in vitro and in vivo experiments. Viable cell counting was employed to assess the toxicity of alumen on Vero cells. The inhibition rate of HSV-2 was defined as the cytopathic effect (CPE) of the cells infected with the virus. Alumen suppositories of different concentrations were vaginally applied to the guinea pigs which were then infected with HSV-2 via a vaginal route. The clinical symptoms were observed and the local virus titer calculated. The results showed that alumen had an in vitro anti-HSV-2 effect by means of antiviral duplication, direct killing of the virus, and antiviral adsorption. Alumen suppositories of different concentrations could reduce or completely inhibit HSV-2 infection in guinea pigs. It was concluded that alumen had an in vitro anti-HSV-2 effect through multiple approaches and it could suppress in vivo vaginal HSV-2 infection of guinea pig to some extent.Journal of Huazhong University of Science and Technology 12/2011; 31(6):828-33. · 0.38 Impact Factor