MUC16 affects the biological functions of ovarian cancer cells and induces an antitumor immune response by activating dendritic cells

BACKGROUND: Ovarian cancer is the 5(th) most common lethal gynecological malignancy with a 5-year survival rate of about 47% and a localized stage diagnosis of 15%, leading to about 125,000 global deaths each year. Therefore, it is urgent to explore novel and effective strategies for radical cure. METHODS: Short hairpin RNA targeting the Mucin16 (MUC16) gene was used to establish MUC16 knockdown in ovarian cancer cells. RT-PCR was performed to quantify the expression of MUC16 mRNA, and western blotting was performed to detect the expression of MUC16 and epithelial-mesenchymal transition-related proteins. Cell counting kit 8 (CCK8) wound healing and transwell assays were performed to assess cell proliferation and cell invasion. Flow cytometry was used to detect CD80-, CD83-, and CD86-expressing dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs) activated by MUC16-pulsed DCs. RESULTS: In this study, we identified MUC16 as a novel target antigen for immunotherapy against ovarian cancer, which was significantly up regulated in ovarian cancer cells and high-grade ovarian serous adenocarcinoma tissues. MUC16 knockdown in Ovcar3 cells using short hairpin RNA targeting the MUC16 gene suppressed the proliferation of migration, invasion, epithelial-mesenchymal transition (EMT), and PI3K/Akt signaling pathway in Ovcar3 cells markedly. MUC16 significantly up-regulated CD80, CD83, and CD86 (mature makers) expression in DCs and T-cell transformation into CD8(+) T-cells detected by Flow cytometry. CONCLUSIONS: For malignant ovarian cancer, MUC16 overexpression promoted cell proliferation, migration, and invasion via the PI3K/AKT signaling pathway. MUC16 pulsing mediated DC maturation and activated CTL response in vitro. Our study offers promising DC-based immunotherapy of considerable clinical value for patients with ovarian cancer.