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.