College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
Chongqing Infectious Disease Medical Center, Chongqing, 400036, China.
Anticancer Agents Med Chem. 2018;18(15):2178-2186. doi: 10.2174/1871520618666180903102630.
Arsenic trioxide (AsO), which has been shown to be effective in treating leukemia and other solid tumors, was strictly restricted in clinical application due to its severe toxicity. The present study was performed to explore whether the combination of AsO and artemisinin could produce a more powerful anticancer effect and reduce the toxicity of AsO.
MTT assay was performed to detect the cell viability of A549, Hela and HepG2 cells treated with AsO and artemisinin. Combination Index (CI) analysis was carried out to evaluate the synergistic effect of AsO and artemisinin. Wound healing assay was performed to evaluate the migration rate. Fluorescent microscopy measurements and flow cytometry were used to evaluate the apoptosis.
Reactive Oxygen Species (ROS) was detected with DCFH-DA. The cell proliferation assay indicated that artemisinin significantly enhanced the inhibitory effect of AsO in a dose and time-dependent manner (P<0.01). Combination Index (CI) analysis further demonstrated that combining artemisinin with AsO generated synergistic effects in A549 (CI=0.65±0.05), Hela (CI=0.68±0.07) and HepG2 (CI=0.47±0.01) cells. The combination of these two drugs also evidently reduced the cell migration rate. Artemisinin also enhanced the apoptosis, necrosis in AsO- treated A549 and Hela cells. Combination of AsO and artemisinin significantly induced more apoptosis (22.1%) than AsO (5.68%) or ART (5.93%) alone in Hela cells. In addition, ROS levels were increased obviously by combining artemisinin with AsO.
The present study indicated that combining artemisinin with AsO would be a novel therapeutic strategy for cancer therapy.
三氧化二砷（AsO）已被证明在治疗白血病和其他实体瘤方面有效，但由于其严重的毒性，在临床应用中受到严格限制。本研究旨在探讨三氧化二砷与青蒿素联合应用是否能产生更强的抗癌作用，并降低三氧化二砷的毒性。
采用 MTT 法检测三氧化二砷和青蒿素处理 A549、Hela 和 HepG2 细胞后的细胞活力。采用组合指数（CI）分析评估三氧化二砷和青蒿素的协同作用。划痕愈合实验评估迁移率。荧光显微镜测量和流式细胞术评估细胞凋亡。
采用 DCFH-DA 检测活性氧（ROS）。细胞增殖实验表明，青蒿素以剂量和时间依赖的方式显著增强了三氧化二砷的抑制作用（P<0.01）。组合指数（CI）分析进一步表明，青蒿素与三氧化二砷联合在 A549（CI=0.65±0.05）、Hela（CI=0.68±0.07）和 HepG2（CI=0.47±0.01）细胞中产生协同作用。两药联合还明显降低了细胞迁移率。青蒿素还增强了三氧化二砷处理的 A549 和 Hela 细胞的凋亡和坏死。与三氧化二砷（5.68%）或青蒿素（5.93%）单独处理相比，三氧化二砷与青蒿素联合处理明显诱导了更多的 Hela 细胞凋亡（22.1%）。此外，联合使用青蒿素和三氧化二砷可明显增加 ROS 水平。
本研究表明，三氧化二砷与青蒿素联合应用可能是一种治疗癌症的新策略。
