Bone Marrow Mesenchymal Stem Cells (BMSCs)-Exosome Inhibits Epithelial Ovarian Cancer (EOC) Cell Proliferative Ability Through Regulating Mitogen-Activated Protein Kinase (MKP)-1 and Mitogen-Activated Protein Kinases (MAPK)/Extracellular-Signal-Regulated Kinase (ERK) Signal Pathway

The BMSCs-exosome plays a role in regulating tumor micro-environment so as to affect tumor cell biological behaviors. However, whether it affects the biological characteristics of epithelial ovarian cancer (EOC) cells remains unclear. Our study aimed to discuss whether BMSCs-exosome affects EOC cell proliferative ability. BMSCs cells were cultivated to isolate exosome which was used to treat EOC cells at different concentrations (25, 50, and 100 μmol/L) followed by measuring cell proliferation by CCK-8, cell invasion and migration by Transwell, MKP-1and MAPK/ERK protein level by Western Blot. BMSCs-exosome showed positive expression of CD9, CD63 and CD81 and negative CD116 and CD19. It could significantly inhibit EOC cell proliferation, invasion and migration in a dose-dependent manner along with reduced expression of MAPK/ERK. In conclusion, BMSCs-exosome inhibits EOC cell biological behaviors possibly through regulation of MKP-1 and MAPK/ERK signal pathway, indicating that it might be used as a novel approach for treating EOC.

Cripto-1/Glucose-Regulated Protein 78 Affects Proliferation, Migration and Apoptosis of Ovarian Carcinoma Cells

Background: The Cripto-1 (CR-1)/glucose-regulated protein 78 (GRP78) complex was involved in enhancing survival in different types of cells. CR-1 presented increased levels in ovarian carcinoma tissue. However, the potential mechanism of CR-1/GRP78 was unclear in ovarian cancer. Thus, the study aimed to analyze the role of CR-1/GRP78 in ovarian carcinoma cells. Methods and materials: The CR-1 and GRP78 expression in different ovarian cancer cell lines were detected by RT-qPCR and Western blot (WB). Immunoprecipitation assay was performed to analyze whether Cripto-1 interacted with GRP78. The CR-1 interfering plasmids or GRP-78 overexpressing plasmids transfected into cells were used to decrease endogenous CR-1 levels and increase GRP-78 levels. Cell clonogenicity and proliferation capabilities were separately evaluated by clone growth assay, along with the detection of cell migration and invasion abilities by transwell and wound healing assay. In addition, Matrix Metalloproteinases (MMPs) levels were detected by WB. The cell apoptosis was analyzed by Flow Cytometer and the detection of apoptosis-related proteins. Results: The results showed that CR-1 and GRP78 levels were higher in SKOV3 than other cell lines. Furthermore, CR-1 interacted with GRP78 in cells, which formed protein complex. CR-1 silence significantly decreased GRP-78 levels. Moreover, GRP78 overexpression blocked the anti-survival effects caused by CR-1 knockdown. Conclusion: CR-1 silence inhibited cell proliferation and promoted apoptosis via GRP78. It replied that GRP-78 overexpression might enhance the biological functions of CR-1/GRP78 complex ameliorated by CR-1 silence. Thus, CR-1/GRP78 could be a potential target for treating ovarian carcinoma.