title: 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.
abstract: 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 seems 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, JHU-011, JHU-013, and JHU-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 with the single treatment regimens. A half-dose of daily Sal-B (40 mg/kg/d) and celecoxib (2.5 mg/kg/d) significantly inhibited JHU-013 xenograft growth relative to mice treated with a full dose of Sal-B or celecoxib alone. The combination was 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 celecoxib holds potential as a new preventive strategy in targeting inflammatory-associated tumor development.
authors.affiliation: Department of Oral Diagnostic Service, Howard University College of Dentistry, NW, Washington, DC 20059, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yubin
authors.initials: Y
authors.lastname: Hao
authors.forename: Hongguang
authors.initials: H
authors.lastname: Ji
authors.forename: Yayin
authors.initials: Y
authors.lastname: Fang
authors.forename: Yinhan
authors.initials: Y
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Sha
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Pang
authors.forename: William M
authors.initials: WM
authors.lastname: Southerland
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
authors.forename: Xinbin
authors.initials: X
authors.lastname: Gu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D000068579:Celecoxib; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology / Q000637:transplantation; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015232:Dinoprostone / Q000097:blood; D004357:Drug Synergism; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D027561:Salvia miltiorrhiza; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D053630:Depsides
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001572:Benzofurans; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors; D015232:Dinoprostone; D011720:Pyrazoles; D013449:Sulfonamides; C076944:salvianolic acid B; D053630:Depsides