Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Fenglin Road, Shanghai 200032, China.
Evid Based Complement Alternat Med. 2012;2012:908601. doi: 10.1155/2012/908601. Epub 2012 Dec 20.
We investigated the effect of Chinese herbal compound Song-you Yin on HCC stemness. MHCC97H and Hep3B cell lines were pretreated with SYY for 4 weeks, and their chemosensitivity to oxaliplatin was evaluated. The expression of CSC-related markers, cell invasion and migration, and colony formation were also examined. SYY-treated orthotopic nude mouse models of human HCC were developed to explore the effect of oxaliplatin on tumor growth, metastasis, and survival. The CSC-related molecular changes in vivo were also evaluated. The result showed that MHCC97H and Hep3B cells pretreated with SYY showed significantly increased chemosensitivity to oxaliplatin and the downregulation of CSC-related markers CD90, CD24, and EPCAM. SYY also attenuated cell motility, invasion, and colony formation in MHCC97H and Hep3B cell lines. The reduced tumorigenicity and pulmonary metastasis were observed in SYY-pretreated cell lines. Combination treatment with oxaliplatin and SYY significantly reduced tumor volume and pulmonary metastasis and prolonged survival compared with oxaliplatin treatment alone. Immunohistochemical analysis showed reduced expression of CD90, ABCG2, ALDH, CD44, EPCAM, vimentin, and MMP-9 and increased the expression of E-cadherin, in HCC cells following combination treatment. These data clearly demonstrate that SYY renders hepatocellular carcinoma sensitive to oxaliplatin through the inhibition of stemness.
我们研究了中药复方“松友饮”对肝癌干细胞特性的影响。MHCC97H 和 Hep3B 细胞系用 SYY 预处理 4 周，评估其对奥沙利铂的化疗敏感性。还检测了 CSC 相关标志物的表达、细胞侵袭和迁移以及集落形成。建立 SYY 处理的人 HCC 原位裸鼠模型，以探讨奥沙利铂对肿瘤生长、转移和生存的影响。还评估了体内 CSC 相关的分子变化。结果表明，用 SYY 预处理的 MHCC97H 和 Hep3B 细胞对奥沙利铂的化疗敏感性显著增加，且 CSC 相关标志物 CD90、CD24 和 EPCAM 的表达下调。SYY 还减弱了 MHCC97H 和 Hep3B 细胞系中的细胞迁移、侵袭和集落形成。在 SYY 预处理的细胞系中观察到肿瘤生成和肺转移减少。与单独奥沙利铂治疗相比，奥沙利铂和 SYY 的联合治疗显著降低了肿瘤体积和肺转移，并延长了生存时间。免疫组织化学分析显示，联合治疗后 HCC 细胞中 CD90、ABCG2、ALDH、CD44、EPCAM、波形蛋白和 MMP-9 的表达减少，E-钙黏蛋白的表达增加。这些数据清楚地表明，SYY 通过抑制干细胞特性使肝癌对奥沙利铂敏感。
