Study On The Interaction Between In Ovarian Cancer Cell Metastasis And Mechanism Of SDF-1-CXCR4 And HIF-1

BackgroudOvarian cancer is one of malignant tumors of the female reproductive system,it has a high rate of mortality, high invasive and metastatic are the main factors leading to poor patients after. About 75% of the patients after the diagnosis has been advanced, because patients have distant metastasis, resulting in the treatment of intractable, patients have lost the best time for treatment prognosis. Therefore, to understand the mechanism of metastasis of ovarian cancer in the clinical treatment and improve the prognosis of the patients is very important.Tumor metastasis is a complex process of multi factors, chemokines in this process plays a very important role. Stromal cell derived factor-1 also known as CXCR12 as a member of the chemokine family, has become a hot and key research in recent years.Mainly SDF- 1 and its corresponding receptor CXCR4 in combination with induced ovarian cancer metastasis process,this process is mainly due to the activation of p38MAPK/ PI-3K signaling pathway downstream. P38MAPK/ PI-3K signal pathway is regarded as a classic signal pathway in the process of tumor metastasis, Hypoxia inducible factor-1(hypoxia inducible factor-1, HIF-1) to play its role also rely on this pathway。So our experimental research interaction and the mechanism of SDF- 1- CXCR4 and HIF- 1 in ovarian cancer cell metastasis, which provides new thinking for the clinical treatment ofovarian cancer.This experiment mainly study the related function of SDF- 1 and HIF- 1 in ovarian cancer and its mechanism, for the first time the two linked in ovarian cancer, This study proved that both in ovarian cancer tissues were positively correlated, and studied the specific pathways, clarified the mechanism of action between.Objective1. Is expression of SDF- 1 αand HIF- 1 αin ovarian cancer tissue related? 2. Would SDF- 1- CXCR4 biological axis activate the expression of HIF? 3. Would the increase of HIF- 1 transcription and expression promote the expression of CXCR4? 4. Is SDF-1 on the activation of PI3K/AKT, MAPK signaling pathway and the role of HIF consistent? 5. Would HIF further promote the expression of CXCR4 and VEGF to promote cell migration?Methods1. Immune histochemical method detect the expression of SDF- 1 and HIF – 1 in ovarian cancer tissues,Real-time quantitative RT-PCR detect HIF- 1 m RNA level in each cell group 2. Western blot tests expression level of AKT/p-AKT, p-38 lightning/p-p38, HIF-1α, CXCR4 in cells. 3. ELISA to detect the content of VEGF 4. Tranwell hit a small room, scratch test each cell migration.Results1. There was positive correlation between the expressions of SDF-1α and HIF-1α in ovarian cancer tissues(r=0.475,P<0.01)q RT-PCR results show that, with the addition of exogenous SDF-1 and the amount of time increases, HIF-1 m RNA levels increased in turn(P<0.05) 2. Western-blot analysis showed that in control, control +SDF-1, control +CXCR4 blocking antibodies groups, p-AKT, p-p38 amount of control +SDF-1 was significantlyincreased(P < 0.01); In control, control +SDF-1, control +CXCR4 blocking antibodies, alpha + LY294002 groups, HIF-1 level significantly increased(P < 0.01);in control + SDF-1 and ovarian cancer cells transfected with HIF sh RNA + SDF-1 alpha two group, CXCR4 of control + SDF-1 group significantly increased(P < 0.01). 3. ELISA detection results show that, control + SDF-1, ovarian cancer cells transfected with HIF sh RNA + SDF-1 alpha two group, VEGF in control + SDF-1 group significantly increased(P < 0.05). 4. Tranwell invasion assay results: SDF-1 group compared with the blank group and the control group of HIF sh RNA + SDF-1 significantly increased, with significant difference(P<0.01). 5. Scratch results: for 12 h, 24 h, 36 h after the scratch distance analysis of SDF-1 group compared with the blank group and the control group of HIF sh RNA + SDF-1 significantly increased, with significant difference(P<0.05).Conclusion1. SDF- 1α and HIF- 1 αexpression in ovarian cancer tissue is related 2. SDF- 1- CXCR4 biological axis will activate the expression of HIF-1α 3. SDF-1 promotes PI3K/AKT, MAPK signal pathway and HIF-1 activation 4. HIF-1 promotes the expression of CXC4 and VEGF to promote cell migration...