Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
Cancer Sci. 2019 Aug;110(8):2676-2683. doi: 10.1111/cas.14036. Epub 2019 Jun 28.
Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are the most common types of liposarcoma. Although WDLPS and DDLPS patients receive intensive treatment including radical surgery and systemic therapy, their overall 5-year survival rates are 90% and 30%, respectively, indicating that DDLPS is clinically more aggressive. We examined whether adipogenic stimulation induces adipogenesis in human WDLPS/DDLPS cells by using dexamethasone, indomethacin, insulin, and 3-isobutyl-1-methylxanthine (IBMX), all putative medications or drugs. Functional in vitro experiments showed that treatment with these four compounds induced adipogenic potency by transcriptional and translational upregulation of genes related to the maintenance of stemness and adipogenic differentiation. Using in vivo xenograft models, we found that the induction of stemness and adipogenesis inhibited the tumorigenic potency of DDLPS. This study suggests a potential application of drug repositioning in which adipogenesis-inducing compounds could be used to treat DDLPS patients in a clinical setting.
高分化脂肪肉瘤 (WDLPS) 和去分化脂肪肉瘤 (DDLPS) 是最常见的脂肪肉瘤类型。尽管 WDLPS 和 DDLPS 患者接受了包括根治性手术和系统治疗在内的强化治疗，但他们的总体 5 年生存率分别为 90%和 30%，这表明 DDLPS 在临床上更具侵袭性。我们通过使用地塞米松、吲哚美辛、胰岛素和 3-异丁基-1-甲基黄嘌呤 (IBMX) 检查了脂肪生成刺激是否会诱导人 WDLPS/DDLPS 细胞发生脂肪生成，这些都是潜在的药物或药物。功能体外实验表明，用这四种化合物处理可通过维持干性和脂肪生成分化的基因的转录和翻译上调诱导脂肪生成能力。使用体内异种移植模型，我们发现干性和脂肪生成的诱导抑制了 DDLPS 的致瘤能力。这项研究表明了药物重新定位的一种潜在应用，即用诱导脂肪生成的化合物在临床环境中治疗 DDLPS 患者。
