Combination effects of salvianolic acid B with low-dose celecoxib on inhibition of head and neck squamous cell carcinoma growth in vitro and in vivo.
Combination effects of salvianolic acid B with low-dose celecoxib on inhibition of head and neck squamous cell carcinoma growth in vitro and in vivo.
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DOI：
10.1158/1940-6207.capr-09-0243
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Gu X
中科院分区：
文献类型：
--
作者：
Zhao Y;Hao Y;Ji H;Fang Y;Guo Y;Sha W;Zhou Y;Pang X;Southerland WM;Califano JA;Gu X
头颈部鳞状细胞癌(HNSCC)的发生与炎症密切相关。环氧合酶-2(COX-2)是一种重要的炎症介质。因此，环氧合酶-2的选择性抑制剂塞来昔布被认为是一种很有前途的HNSCC化学预防药物。剂量依赖性的心脏毒性限制了塞来昔布的长期使用，但似乎可以通过降低剂量来减少这种毒性。我们发现从丹参中分离得到的丹酚酸B(SAL-B)能有效抑制COX-2的表达并诱导多种癌细胞的凋亡。在这项研究中，我们报告了SAL-B与低剂量塞来昔布联合治疗HNSCC比单独使用任何一种药物都有更显著的抗癌作用。在四种HNSCC细胞系(JHU-06、-011、-013和-022)中，通过评估细胞活力、增殖和肿瘤异种移植生长来评估联合作用。联合用药和单独用药均显著抑制细胞的存活和增殖。然而，与单一治疗方案相比，联合治疗显著增强了JHU-013和JHU-022细胞株的抗癌效果。Sal-B(40 mg/kg/d)和塞来昔布(2.5 mg/kg/d)半量给药可显著抑制JHU-013移植瘤的生长，与全量Sal-B或塞来昔布单独给药相比。联合应用不仅能显著抑制COX-2的表达，还能增强对细胞凋亡的诱导作用。综上所述，这些结果有力地表明，多功能抗癌药SAL-B与低剂量塞来昔布联合应用，在针对炎性相关肿瘤发展方面具有潜在的新的预防策略。
Head and neck squamous cell carcinoma (HNSCC) development is closely associated with inflammation. Cyclooxygenase-2 (Cox-2) is an important mediator of inflammation. Therefore, celecoxib, a selective inhibitor of COX-2, was hailed as a promising chemopreventive agent for HNSCC. Dose-dependent cardiac toxicity limits long term use of celecoxib, but it appears likely that this may be diminished by lowering its dose. We found that salvianolic acid B (Sal-B), isolated from Salvia miltiorrhiza Bge, can effectively suppress COX-2 expression and induce apoptosis in a variety of cancer cell lines. In this study, we report that combination of Sal-B with low dose celecoxib results in a more pronounced anticancer effect in HNSCC than either agent alone. The combination effects were assessed in four HNSCC cell lines (JHU-06, -011, -013 and -022) by evaluating cell viability, proliferation, and tumor xenograft growth. Cell viability and proliferation were significantly inhibited by both the combined and single agent treatments. However, the combination treatment significantly enhanced anticancer efficacy in JHU-013 and JHU-022 cell lines compared to the single treatment regimens. A half dose of daily Sal-B (40mg/kg/day) and celecoxib (2.5mg/kg/day) significantly inhibited JHU-013 xenograft growth, relative to mice treated with a full dose of Sal-B or celecoxib alone. The combination was not only associated with profound inhibition of COX-2, and enhanced induction of apoptosis. Taken together, these results strongly suggest that combination of Sal-B, a multifunctional anticancer agent, with low dose of celecoxib hold potential as a new preventive strategy in targeting inflammatory associated tumor development.