GOLPH3 Regulates The Proliferation And Apoptosis Of Epithelial Ovarian Cancer Cells Via The PI3K/AKT Signaling Pathway

Ovarian cancer is the most deadly of female genital tumors and is a huge threat to the lives and health of many women.Epithelial ovarian cancer（EOC）is the most common type of ovarian cancer,accounting for about 70 percent of all ovarian cancers.The early symptoms of ovarian cancer are very hidden,and the late stage is easy to be widely transferred to abdominal organs,and chemotherapy resistance is easy to be generated during treatment,so its treatment efficiency and survival rate are very low.The enhancement of the ability of ovarian malignant tumors to proliferate,invade and metastasize is its characteristic biological behavior and its important pathogenesis.Therefore,a thorough understanding of ovarian malignant tumor cell biology characteristics,to explore the pathogenesis of tumor,looking for gene therapy targets,not only can improve the early diagnosis of ovarian malignant tumors,also can improve the survival rate.Golgi phosphoprotein 3（GOLPH3）is a newly discovered oncogene.Recent studies have shown that GOLPH3 is highly expressed in a variety of malignant tumors and is closely related to tumor value-added invasion and poor prognosis.However,little is known about the biological and molecular mechanisms of GOLPH3 in epithelial ovarian cancer.Therefore,the purpose of this study is to explore the effect and mechanism of GOLPH3 gene on cell proliferation and apoptosis of epithelial ovarian cancer cells and to find new gene therapy targets.PartⅠ,we used immunohistochemical techniques to detect epithelial ovarian cancer tissue and normal ovarian tissues surrounding the ovarian benign tumor of GOLPH3 and PI3K/Akt signaling pathway related molecules(Akt,p-Akt³⁰⁸,p-Akt⁴⁷³),and the results:The expression of GOLPH3 gene and p-Akt³⁰⁸,p-Akt⁴⁷³ in epithelial ovarian cancer tissues are high,and GOLPH3 with p-Akt³⁰⁸,p-Akt⁴⁷³ have correlation（R1=0.57,p<0.05;R2=0.55,P<0.55）.PartⅡ,siRNA was used to interfere with GOLPH3 gene,and after its expression was down-regulated,The proliferation of ovarian cancer cells was detected by MTT,Flow cytometry to detect ovarian cancer cell apoptosis.The results showed that SKOV3proliferation decreased and apoptosis increased after the expression of GOLPH3 gene was down-regulated.PartⅢ,the expression of GOLPH3gene was down-regulated by siRNA interference.The protein expression of Akt,p-Akt⁴⁷³,p-Akt³⁰⁸ and bcl-2 related genes of PI3K/Akt signaling pathway was detected by Western Blot.Then,ovarian cancer SKOV3 cells were treated with the P13K/Akt signaling pathway inhibitor LY294002.Western Blot was used to detect the protein expression of Akt,p-Akt⁴⁷³,p-Akt³⁰⁸ and Bcl-2.Results:（1）After the small interfering RNA silenced the expression of GOLPH3 in SKOV3 cells,Western Blot,according to the results of p-Akt⁴⁷³,p-Akt³⁰⁸,antiapoptotic gene Bcl-2 protein expression level decreased,and there was no significant difference in the expression levels of Akt protein.（2）After the treatment of SKOV3 cells by the P13K/Akt signaling pathway inhibitor LY294002,Western Blot results showed that the protein expression levels of p-Akt⁴⁷³,p-Akt³⁰⁸ and anti-apoptosis gene Bcl-2 all decreased,and there was no statistically significant difference in the expression levels of Akt protein.（3）After treating SKOV3 cells with the P13K/Akt signaling pathway inhibitor LY294002,the results of flow cytometry showed that the apoptosis of ovarian cancer increased.The results of MTT assay showed that the proliferation of ovarian cancer decreased.Conclusion:GOLPH3 can affect the proliferation and apoptosis of epithelial ovarian cancer cells by activating the PI3K/Akt signaling pathway.