Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D‑72076 Tuebingen, Germany.
Department of Surgery, Kantonsspital Münsterlingen, CH‑8596 Münsterlingen, Switzerland.
Int J Oncol. 2021 Feb;58(2):266-274. doi: 10.3892/ijo.2020.5155. Epub 2020 Dec 10.
Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, has an unfavorable outcome in advanced tumor stages with less than 30% failure‑free survival. Curcumin (CUR) is a promising drug in complementary oncology with few side effects but proven efficacy in various adult oncological entities. The present study analyzed the effects of CUR on pediatric (RMS) cell lines in vitro. RMS cell lines (RD and RH30), and skeletal muscle cells (SKMC) were treated with different doses of CUR (1.5‑30 µM) alone, with phototherapy (PDT, 488 nm) or in combination with vincristine (VCR) or dactinomycin (DAC). MTT assays were used for analysis of RMS tumor cell viability. Clonal cell growth was assessed via colony forming assays and migration of the cells was analyzed with scratch tests. Annexin V staining was used to determine apoptosis in flow cytometry. Possible RMS resistance towards CUR after long‑term treatment was analyzed with MTT assays. CUR decreased cell viability in all assessed RMS cell lines in a concentration‑dependent manner with IC50=14‑20 µM. CUR enhanced the effects of the cytotoxic drugs VCR or DAC, and led to reduced migration and increased cell apoptosis. In combination with PDT, CUR decreased the cell viability in minute quantities with up to a 10‑fold lower IC50 than without PDT. CUR effectively inhibited the malignant properties of pediatric RMS cells and should be focused on as a useful additional agent in standard chemotherapy of RMS in children.
横纹肌肉瘤(RMS)是最常见的小儿软组织肉瘤,在晚期肿瘤中预后不良,无失败生存的患者少于 30%。姜黄素(CUR)是一种很有前途的药物,在补充肿瘤学方面具有很少的副作用,但在各种成人肿瘤实体中已被证明具有疗效。本研究分析了 CUR 对小儿(RMS)细胞系的体外作用。用不同剂量的 CUR(1.5-30μM)单独处理 RMS 细胞系(RD 和 RH30)和骨骼肌细胞(SKMC),用光疗(PDT,488nm)或联合长春新碱(VCR)或放线菌素 D(DAC)处理。MTT 法用于分析 RMS 肿瘤细胞活力。通过集落形成实验评估克隆细胞生长,通过划痕实验分析细胞迁移。用 Annexin V 染色法通过流式细胞术检测细胞凋亡。用 MTT 法分析 RMS 对 CUR 的长期治疗后可能产生的耐药性。CUR 以浓度依赖性方式降低所有评估的 RMS 细胞系中的细胞活力,IC50=14-20μM。CUR 增强了细胞毒药物 VCR 或 DAC 的作用,并导致迁移减少和细胞凋亡增加。与 PDT 联合使用时,CUR 以低至 10 倍的 IC50 即可在微量下降低细胞活力,而无需 PDT。CUR 有效抑制了小儿 RMS 细胞的恶性特性,应作为小儿 RMS 标准化疗的有用辅助药物。