Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China.
Laboratory of Tumor Angiogenesis and Microenvironment, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China.
Mol Med Rep. 2019 Mar;19(3):1501-1508. doi: 10.3892/mmr.2019.9814. Epub 2019 Jan 3.
Bone morphogenetic protein 9 (BMP9) belongs to the transforming growth factor‑β (TGF‑β) superfamily, and has been reported to promote cancer cell proliferation and epithelial‑mesenchymal transition (EMT). Cisplatin (DDP) is the first line treatment for ovarian cancer. However, initiation of EMT confers insensitivity to chemotherapy. The present study aimed to verify and examine the mechanisms underlying the effects of BMP9 on treatment with DDP for ovarian cancer. Prior to treatment with DDP, ovarian cancer cells were exposed to BMP9 for 3 days. Following this, cell viability, apoptosis rate and the extent of DNA damage were evaluated to compare the effects of DDP on BMP9‑pretreated and non‑pretreated ovarian cancer cells. In addition, EMT marker expression was evaluated by western blotting and immunofluorescence. The results demonstrated that BMP9 pretreatment inhibited the cytotoxicity of DDP on ovarian cancer cells. Additionally, BMP9‑pretreated ovarian cancer cells had downregulated expression of the epithelial marker E‑cadherin, which was accompanied by an upregulation of the mesenchymal markers N‑cadherin, Snail, Slug, and Twist. Taken together, the findings of the present study indicated that BMP9 conferred resistance to DDP in ovarian cancer cells by inducing EMT. The present study provided valuable insight into the mechanisms of chemotherapy in ovarian cancer and highlighted the potential of BMP9 as a novel therapeutic target for improving cisplatin chemosensitivity.
骨形态发生蛋白 9（BMP9）属于转化生长因子-β（TGF-β）超家族，据报道可促进癌细胞增殖和上皮间质转化（EMT）。顺铂（DDP）是治疗卵巢癌的一线药物。然而，EMT 的启动会导致对化疗的不敏感。本研究旨在验证和研究 BMP9 对卵巢癌细胞 DDP 治疗的影响及其机制。在 DDP 治疗前，用 BMP9 处理卵巢癌细胞 3 天。然后，评估细胞活力、细胞凋亡率和 DNA 损伤程度，以比较 DDP 对 BMP9 预处理和未预处理的卵巢癌细胞的作用。此外，通过 Western blot 和免疫荧光评估 EMT 标志物的表达。结果表明，BMP9 预处理抑制了 DDP 对卵巢癌细胞的细胞毒性。此外，BMP9 预处理的卵巢癌细胞中上皮标志物 E-钙黏蛋白的表达下调，同时间充质标志物 N-钙黏蛋白、Snail、Slug 和 Twist 的表达上调。综上所述，本研究结果表明，BMP9 通过诱导 EMT 赋予卵巢癌细胞对 DDP 的耐药性。本研究为卵巢癌化疗机制提供了有价值的见解，并强调了 BMP9 作为提高顺铂化疗敏感性的新治疗靶点的潜力。
