DMBT1 suppresses cell proliferation, migration and invasion in ovarian cancer and enhances sensitivity to cisplatin through galectin-3/PI3k/Akt pathway

Ovarian cancer (OC) is one of the most common gynaecologic malignancies. Deleted in malignant brain tumors 1 (DMBT1) was considered as a tumour suppressor in multiple cancers, but there have been no systemic profiling studies of DMBT1 in OC until now. The aim of this study is to explore the role and the potential mechanism of DMBT1 in OC. mRNA levels and protein expressions of corresponding genes were detected by quantitative real-time polymerase chain reaction and western blot. Cell proliferation was detected by CCK-8 assay and cell colony formation. Cell migration and invasion were detected by wound healing and transwell assay. The combination between DMBT1 and galectin-3 was demonstrated by immunoprecipitation. We demonstrated that DMBT1 was downregulated in OC cell lines, especially SKOV3 cells. Overexpression of DMBT1 significantly inhibited cell proliferation, colony formation, migration and invasion, as well as decreased Matrix Metalloproteinase-2 (MMP-2) and MMP-7. DMBT1 caused a reduction of cell viability by treatment with cisplatin. Immunoprecipitation assay revealed a combination between DMBT1 and galectin-3. DMBT1 could decrease the expression of galectin-3 and inhibit the phosphorylation of PI3K and AKT, while overexpression of galectin-3 reversed this effect. In summary, DMBT1 might inhibit the progression of OC and improve the sensitivity of SKOV3 cells to cisplatin through galectin-3/PI3K/AKT pathway, giving a new insight into the role of DMBT1 in OC and enriching the potential strategies for OC treatment. Significance of the Study The present study focus on the role and the potential mechanism of DMBT1 in ovarian cancer (OC). We demonstrated that DMBT1 might inhibit the progression of ovarian by inhibiting cell proliferation, migration and invasion and increased the sensitivity to cisplatin through galectin-3/PI3K/AKT pathway. The findings ensure the interaction relation between DMBT1 and galectin-3 in OC, providing a novel biological marker for OC and enriching the potential strategies for OC treatment.