Lin Xiaochang, Yi Zhiyong, Diao Jianxin, Shao Meng, Zhao Liang, Cai Hongbing, Fan Qin, Yao Xueqing, Sun Xuegang
Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
J Transl Med. 2014 Apr 26;12:105. doi: 10.1186/1479-5876-12-105.
Shaoyao decoction (SYD) is a traditional Chinese medicine prescription formulated by Liu Wan-Su, a master of traditional Chinese medicine in Jin-Yuan Dynasty. SYD is effective in treating ulcerative colitis. Paeonol, a component of SYD, inhibits colorectal cancer (CRC) cell proliferation and induces CRC cell apoptosis. In this study, azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated CRC (caCRC) model and CRC cell lines were used to examine the effects of SYD on CRC in vivo and in vitro.
A translational medicine strategy based on phytomics quality control was adopted. Liquid chromatography was employed for the chemical characterization and chemical fingerprinting of SYD. Protein expression and macrophage existence were determined by immunohistochemistry and western blot. Serum cytokines were quantified by Luminex assay.
AOM/DSS-induced caCRC phenotypically resembled human caCRC. SYD significantly increased the survival rate of the mice, ameliorated the general well-being of the mice, and reduced the incidence and multiplicity of colonic neoplasms. SYD inhibited epithelial-mesenchymal transition (EMT), as indicated by upregulated epithelia cadherin and downregulated neuronal cadherin, fibronectin, vimentin, and transcription factor Snail. SYD reduced the expression levels of serum interleukin 1β, interleukin-6, tumor necrosis factor α, tumor-associated macrophages, and p65. These results showed that SYD can attenuate proinflammatory cytokines and inhibit EMT.
SYD ameliorates caCRC by suppressing inflammation and inhibiting EMT. SYD might be an alternative therapy for caCRC.
芍药汤（SYD）是金元时期中医大师刘完素所创制的中药方剂。芍药汤在治疗溃疡性结肠炎方面疗效显著。芍药汤的成分之一丹皮酚可抑制结直肠癌（CRC）细胞增殖并诱导CRC细胞凋亡。在本研究中，采用氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导的结肠炎相关结直肠癌（caCRC）模型和CRC细胞系，来研究芍药汤在体内和体外对CRC的影响。
采用基于植物组学质量控制的转化医学策略。运用液相色谱法对芍药汤进行化学表征和化学指纹图谱分析。通过免疫组织化学和蛋白质印迹法测定蛋白质表达和巨噬细胞存在情况。采用Luminex检测法对血清细胞因子进行定量分析。
AOM/DSS诱导的caCRC在表型上类似于人类caCRC。芍药汤显著提高了小鼠的存活率，改善了小鼠的整体健康状况，并降低了结肠肿瘤的发生率和多发性。芍药汤抑制上皮-间质转化（EMT），表现为上皮钙黏蛋白上调，神经钙黏蛋白、纤连蛋白、波形蛋白和转录因子Snail下调。芍药汤降低了血清白细胞介素1β、白细胞介素-6、肿瘤坏死因子α、肿瘤相关巨噬细胞和p65的表达水平。这些结果表明，芍药汤可减轻促炎细胞因子并抑制EMT。
芍药汤通过抑制炎症和抑制EMT来改善caCRC。芍药汤可能是caCRC的一种替代疗法。
