Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivo via cyclooxygenase-2 and apoptotic pathways.
Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivo via cyclooxygenase-2 and apoptotic pathways.
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DOI：
10.1002/ijc.24160
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发表时间：
2009-05-01
影响因子：
6.4
通讯作者：
Giu, Xinbin
中科院分区：
文献类型：
--
作者：
Hao, Yubin;Xie, Tianpei;Korotcov, Alexandru;Zhou, Yanfei;Pang, Xiaowu;Shan, Liang;Ji, Hongguang;Sridhar, Rajagopalan;Wang, Paul;Califano, Joseph;Giu, Xinbin
口腔黏膜中环氧合酶-2（考克斯-2）的过度表达与头颈部鳞状细胞癌（HNSCC）的风险增加有关。塞来昔布是一种非甾体抗炎药，抑制考克斯-2，但不抑制考克斯-1。这种选择性的考克斯-2抑制剂有望成为癌症预防剂。对塞来昔布心脏毒性的担忧限制了其在长期化学预防和治疗中的应用。丹酚酸B（Sal-B）是丹参的主要生物活性成分，在我国用于治疗肿瘤和慢性炎症性疾病。本研究的目的是探讨Sal-B抑制HNSCC生长的机制。采用溶剂提取和两步色谱法从丹参中分离得到Sal-B。通过估计考克斯-2表达、细胞活力和半胱天冬酶依赖性细胞凋亡来评估Sal-B在HNSCC和其他细胞系中的药理学活性。Sal-B抑制HNSCC JHU-022和JHU-013细胞的生长，IC50分别为18和50 µ M。用Sal-B（80 mg/kg/天）或塞来昔布（5 mg/kg/天）处理具有HNSCC实体瘤异种移植物的裸鼠25天，以研究考克斯-2抑制剂的体内作用。Sal-B治疗组的肿瘤体积显著低于塞来昔布治疗组或未治疗对照组（p <0.05）。Sal-B抑制培养的HNSCC细胞和从肿瘤异种移植物分离的HNSCC细胞中的考克斯-2表达。Sal-B还引起前列腺素E2合成的剂量依赖性抑制，无论是否有脂多糖刺激。综上所述，Sal-B显示出作为考克斯-2靶向抗癌剂用于HNSCC预防和治疗的前景。
Overexpression of cyclooxygenase-2 (COX-2) in oral mucosa has been associated with increased risk of head and neck squamous cell carcinoma (HNSCC). Celecoxib is a non steroidal anti-inflammatory drug, which inhibits COX-2 but not COX-1. This selective COX-2 inhibitor holds promise as a cancer preventive agent. Concerns about cardiotoxicity of celecoxib, limits its use in long term chemoprevention and therapy. Salvianolic acid B (Sal-B) is a leading bioactive component of Salvia miltiorrhiza Bge, which is used for treating neoplastic and chronic inflammatory diseases in China. The purpose of this study was to investigate the mechanisms by which Sal-B inhibits HNSCC growth. Sal-B was isolated from Salvia miltiorrhiza Bge by solvent extraction followed by two chromatographic steps. Pharmacological activity of Sal-B was assessed in HNSCC and other cell lines by estimating COX-2 expression, cell viability and caspase-dependent apoptosis. Sal-B inhibited growth of HNSCC JHU-022 and JHU-013 cells with IC50 of 18 and 50 µM respectively. Nude mice with HNSCC solid tumor xenografts were treated with Sal-B (80mg/kg/day) or celecoxib (5mg/kg/day) for 25 days to investigate in vivo effects of the COX-2 inhibitors. Tumor volumes in Sal-B treated group were significantly lower than those in celecoxib treated or untreated control groups (p<0.05). Sal-B inhibited COX-2 expression in cultured HNSCC cells and in HNSCC cells isolated from tumor xenografts. Sal-B also caused dose-dependent inhibition of prostaglandin E2 synthesis, either with or without lipopolysaccharide stimulation. Taken together, Sal-B shows promise as a COX-2 targeted anticancer agent for HNSCC prevention and treatment.
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