The Relationship Between The Expression And Tumor HIF-1α And MMP-2 In Ovarian Cancer Metastasis

ObjectiveDetecting the expression of Hypoxia-inducible factor-1 alpha(HIF-1α) and matrix metalloproteinase 2(MMP-2) in ovarian tumors,and studying the correlation between HIF-1α and MMP-2 and ovarian tumor metastasis. Method In the study, we chose 81 patients with ovarian tumor getting treatment from January 2007 ~ June 2012 in our hospital. The malignant degree was divided into three groups: ① malignant group: 35 cases including 9 cases of ovarian serous cystadenocarcinoma and 26 cases of ovarian clear cell carcinoma; ② borderline group: 22 cases of borderline ovarian serous cystadenoma; ③the benign group: 24 cases were diagnosed as benign serous cystadenoma of ovary.(1) RT-PCR, Western blot was used to detect the expression of HIF-1 α and MMP-2 in the ovarian cancer cell line HO-8910 and metastasis of ovarian cancer cell line HO-8910-PM;(2) RT-PCR, Western blot, immunehistochemistry was used to detect the expression of HIF-1 α and MMP-2 in ovarian tumor according to the degree of differentiation, tumor staging, invasion and metastasis and analyzed the correlation of HIF-1α and MMP-2 and tumor metastasis.(3) We detected the expression of HIF-1α and MMP-2 and the metastasis of ovarian cancer cell line HO-8910-PM by RT-PCR, Western blot, Immune Histochemistry, MTT, BCA, Wound scratch assay and Transwell assay before and after the treatment of Rapamycin. Results(1) HIF-1 α and low expression of MMP-2 in ovarian cancer cell line HO-8910, high expression in ovarian cancer cell line HO-8910-PM in high metastasis;(2) The expression of HIF-1α and MMP-2 in ovarian malignant tumor group was significantly higher than that in borderline group and benign group, no significant difference between borderline group and benign group; expression in malignant group was increased with the malignant degree of tumor tissue and there was a significant positive correlation trend; With the increase of ovarian tumor differentiation degree and decreased clinical stage, the positive expression rate of HIF-1α and MMP-2 protein were significantly increased; HIF-1α expression and patient age, tumor size, and the depth of tumor invasion, lymph node metastasis were associated; the positive expression of MMP-2 was not associated with age, the size of tumor, depth of tumor invasion, or lymph node metastasis.(3) HIF-1α、MMP-2 play an important role in the invasion and metastasis of ovarian cancer cell line HO-8910-PM in the condition of hypoxia, after treatment of Rapamycin the expression of HIF-1α、MMP-2 was inhibited significantly, and the matastasis of HO-8910-PM cell descreased as well. Conclusion(1) HIF-1α and MMP-2 in ovarian cancer cell lines and tissues were highly expressed, positively correlated with the expression of the two;(2) With the increase the degree of differentiation of ovarian cancer and clinical staging, the positive expression rate of HIF-1α protein and MMP-2 protein were significantly increased; HIF-1α and MMP-2 were expressed in ovarian carcinoma and tumor metastasis.(3) Treatment of Rapamycin inhibited the expression of HIF-1α、MMP-2 significantly, and the matastasis of HO-8910-PM cell was descreased as well.