Deparment of Traditional Chinese Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Sci Rep. 2020 May 18;10(1):8175. doi: 10.1038/s41598-020-64561-9.
Compound Opening Arrow Mixture (COAM) has demonstrated therapeutic effects in patients with breast cancer. We explored the underlying molecular mechanisms of COAM using a mouse model of breast cancer. Luciferase-labeled 4T1-Luc2 cells were inoculated into the breast pad of BALB/c-nu mice, which were divided into model group (saline), COAM (6 g/ml high-dose, 3 g/ml medium-dose, and 1.5 g/ml low-dose) groups, and low-molecular-weight heparin (LMWH, 1500 U/Kg) group. The number and distribution of 4T1-luc2 tumors were measured by an in vivo imaging system. Tumor cell apoptosis was measured through TUNEL and quantitating the expression of Caspase-3 mRNA and protein. Compared with the model group, in vivo tumor growth was lower in the LMWH- and COAM-treated groups. Tumor apoptosis was time-dependent and dose-dependent, as shown by a higher TUNEL apoptotic index and higher Caspase-3 mRNA and Caspase-3/cleaved-Caspase-3 proteins levels on the 14th day than the 7th day. The COAM high-dose group had the highest apoptotic index and the most activation of Caspase-3. Collectively, COAM significantly inhibits the growth of 4T1-luc2 breast cancer in mice and induces tumor apoptosis by activating Caspase-3, which provides a preliminary explanation of therapeutic effects of COAM.
复方开口箭合剂（COAM）在乳腺癌患者中显示出治疗效果。我们使用乳腺癌小鼠模型探讨了 COAM 的潜在分子机制。将荧光素酶标记的 4T1-Luc2 细胞接种到 BALB/c-nu 小鼠的乳腺垫中，将其分为模型组（生理盐水）、COAM 组（高剂量 6g/ml、中剂量 3g/ml 和低剂量 1.5g/ml）和低分子量肝素（LMWH，1500U/Kg）组。通过体内成像系统测量 4T1-luc2 肿瘤的数量和分布。通过 TUNEL 测量肿瘤细胞凋亡，并定量测定 Caspase-3 mRNA 和蛋白的表达。与模型组相比，LMWH 和 COAM 治疗组的体内肿瘤生长较低。肿瘤凋亡呈时间和剂量依赖性，第 14 天的 TUNEL 凋亡指数和 Caspase-3 mRNA 及 Caspase-3/cleaved-Caspase-3 蛋白水平均高于第 7 天。COAM 高剂量组的凋亡指数最高，Caspase-3 的激活最明显。综上所述，COAM 显著抑制了 4T1-luc2 乳腺癌在小鼠中的生长，并通过激活 Caspase-3 诱导肿瘤凋亡，为 COAM 的治疗效果提供了初步解释。
