CXCR4/CXCR7 gene-silencing suppresses ovarian cancercell proliferation and tumour growth through modulationof the CXCL12-CXCR4/CXCR7 chemokine axisand activation of MAPK signalling pathway

IntroductionOvarian cancer is the most common malignant cancer among females. This study aimed to investigate role of the CXCL12-CXCR4/CXCR7 chemokine axis in ovarian cancer.Material and methodsSKOV3 cells were transfected with siCXCR4/siCXCR7 plasmids and divided into SKOV3, LV3, LV3-siCXCR4, and LV3-siCXCR7 groups. Cell viability and apoptosis were examined using MTT and flow cytometry. ELISA was conducted to evaluate vascular-endothelial growth factor-A (VEGF-A), interleukin-6 (IL-6), and interleukin-8 (IL-8) levels. SKOV3 cells were transplanted into mice to establish a Xenograft model. The tumour volume of the Xenograft model was recorded. CD31, matrix-metalloprotein-9 (MMP-9), vimentin, and E-cadherin expressions in SKOV3 cells and tumour tissues were evaluated with quantitative real-time PCR (qRT-PCR) and western blot. Immunohistochemistry assay was used to detect VEGF-A, CD31, MMP-9, vimentin, and E-cadherin expression.ResultsSKOV3 cells strongly expressed CXCR4 and CXCR7. CXCL12 significantly enhanced cell viability, and CXCR4/CXCR7 inhibitor remarkably reduced cell viability of SKOV3 (p < 0.05). CXCR4/CXCR7 gene-silencing significantly decreased SKOV3 viability compared to the SKOV3 or LV3 group (p < 0.05). CXCR4/CXCR7 gene-silencing modulated cell cycle and increased apoptosis rates compared to SKOV3 or LV3 group (p < 0.05). CXCR4/CXCR7 gene-silencing inhibited VEGF-1, IL-6, and IL-8 secretion. CXCR4/CXCR7 gene-silencing modulated levels of CD31, MMP-9, vimentin, and E-cadherin. CXCR4/CXCR7 gene-silencing suppressed p-ERK1/2 (p < 0.05) and strengthened inhibitive effects of CXCR4/CXCR7 inhibitor on p-ERK1/2. CXCR4/CXCR7 gene-silencing reduced tumour volume and regulated tumourigenesis-associated molecules in the mouse Xenograft model.ConclusionsCXCR4/CXCR7 gene-silencing could suppress ovarian cancer cell proliferation and tumour growth through modulation of the CXCL12-CXCR4/CXCR7 chemokine axis and mitogen-activated protein kinase (MAPK) signalling pathway.