Liang Wenquan, Cui Jianxin, Zhang Kecheng, Xi Hongqing, Cai Aizhen, Li Jiyang, Gao Yunhe, Hu Chong, Liu Yi, Lu Yixun, Wang Ning, Wu Xiaosong, Wei Bo, Chen Lin
Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Institute of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Oncotarget. 2017 Nov 17;8(65):109094-109106. doi: 10.18632/oncotarget.22618. eCollection 2017 Dec 12.
Colon cancer is the third most common malignancy worldwide, and chemotherapy is a widely used strategy in clinical therapy. Chemotherapy-resistant of colon cancer is the main cause of recurrence and progression. Novel drugs with efficacy and safety in treating colon cancer are urgently needed. Shikonin, a naphthoquinone derived from the roots of the herbal plant , has been determined to be a potent anti-tumor agent. The aim of the present study was to detect the underlying anti-tumor mechanism of shikonin in colon cancer. We found that shikonin suppressed the growth of colon cancer cells in a dose-dependent manner and . Shikonin induced mitochondria-mediated apoptosis, which was regulated by Bcl-2 family proteins. Shikonin increased the generation of intracellular ROS, which played an upstream role in shikonin-induced apoptosis. Our data indicated that generation of ROS, down-regulated expression of Bcl-2 and Bcl-xL, depolarization of the mitochondrial membrane potential and activation of the caspase cascade were components of the programmed event of shikonin-induced apoptosis in colon cancer cells. In addition, shikonin presented minimal toxicity to non-neoplastic colon cells and no liver injury in xenograft models, showing safety in the control of colon cancer cell growth and . Taken together, our findings suggest that shikonin might serve as a potential novel therapeutic drug in the treatment of human colon cancer.
结肠癌是全球第三大常见恶性肿瘤，化疗是临床治疗中广泛应用的策略。结肠癌的化疗耐药是复发和进展的主要原因。迫切需要具有治疗结肠癌疗效和安全性的新型药物。紫草素是一种从草本植物根部提取的萘醌，已被确定为一种有效的抗肿瘤剂。本研究的目的是检测紫草素在结肠癌中的潜在抗肿瘤机制。我们发现紫草素以剂量依赖的方式抑制结肠癌细胞的生长。紫草素诱导线粒体介导的凋亡，这由Bcl-2家族蛋白调节。紫草素增加细胞内ROS的产生，其在紫草素诱导的凋亡中起上游作用。我们的数据表明，ROS的产生、Bcl-2和Bcl-xL表达的下调、线粒体膜电位的去极化以及半胱天冬酶级联反应的激活是紫草素诱导结肠癌细胞凋亡程序性事件的组成部分。此外，紫草素对非肿瘤性结肠细胞的毒性极小，在异种移植模型中无肝损伤，在控制结肠癌细胞生长方面显示出安全性。综上所述，我们的研究结果表明紫草素可能作为一种潜在的新型治疗药物用于治疗人类结肠癌。
