Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Cell Biochem Funct. 2020 Aug;38(6):801-809. doi: 10.1002/cbf.3549. Epub 2020 May 19.
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.
卵巢癌（OC）是最常见的妇科恶性肿瘤之一。缺失于恶性脑肿瘤 1（DMBT1）在多种癌症中被认为是一种肿瘤抑制因子，但直到现在，还没有对 OC 中 DMBT1 的系统分析研究。本研究旨在探讨 DMBT1 在 OC 中的作用和潜在机制。通过定量实时聚合酶链反应和 Western blot 检测相应基因的 mRNA 水平和蛋白表达。通过 CCK-8 检测和细胞集落形成检测细胞增殖。通过划痕愈合和 Transwell 检测检测细胞迁移和侵袭。通过免疫沉淀证明 DMBT1 与半乳糖凝集素-3 的结合。我们表明 DMBT1 在 OC 细胞系中下调，特别是 SKOV3 细胞。DMBT1 的过表达显着抑制细胞增殖、集落形成、迁移和侵袭，并降低基质金属蛋白酶-2（MMP-2）和 MMP-7。DMBT1 用顺铂处理可降低细胞活力。免疫沉淀实验显示 DMBT1 与半乳糖凝集素-3 结合。DMBT1 可以降低半乳糖凝集素-3 的表达并抑制 PI3K 和 AKT 的磷酸化，而过表达半乳糖凝集素-3 则逆转了这一作用。综上所述，DMBT1 可能通过半乳糖凝集素-3/PI3K/AKT 通路抑制 OC 的进展并提高 SKOV3 细胞对顺铂的敏感性，为 DMBT1 在 OC 中的作用提供了新的见解，并丰富了 OC 治疗的潜在策略。研究的意义：本研究重点研究 DMBT1 在卵巢癌（OC）中的作用和潜在机制。我们表明，DMBT1 可能通过抑制细胞增殖、迁移和侵袭并通过半乳糖凝集素-3/PI3K/AKT 通路增加对顺铂的敏感性来抑制卵巢癌的进展。这些发现确保了 DMBT1 在 OC 中与半乳糖凝集素-3 的相互作用关系，为 OC 提供了一种新的生物标志物，并丰富了 OC 治疗的潜在策略。
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