Martin C K, Dirksen W P, Carlton M M, Lanigan L G, Pillai S P, Werbeck J L, Simmons J K, Hildreth B E, London C A, Toribio R E, Rosol T J
Department of Veterinary Biosciences, College of Veterinary Medicine, Columbus, OH, USA.
Small Animal Imaging Center Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Vet Comp Oncol. 2015 Sep;13(3):203-17. doi: 10.1111/vco.12037. Epub 2013 May 8.
Oral squamous cell carcinoma (OSCC) is common in cats and humans and invades oral bone. We hypothesized that the cyclooxygenase (COX)-2 inhibitor, meloxicam, with the bisphosphonate, zoledronic acid (ZOL), would inhibit tumour growth, osteolysis and invasion in feline OSCC xenografts in mice. Human and feline OSCC cell lines expressed COX-1 and COX-2 and the SCCF2 cells had increased COX-2 mRNA expression with bone conditioned medium. Luciferase-expressing feline SCCF2Luc cells were injected beneath the perimaxillary gingiva and mice were treated with 0.1 mg kg(-1) ZOL twice weekly, 0.3 mg kg(-1) meloxicam daily, combined ZOL and meloxicam, or vehicle. ZOL inhibited osteoclastic bone resorption at the tumour-bone interface. Meloxicam was more effective than ZOL at reducing xenograft growth but did not affect osteoclastic bone resorption. Although a synergistic effect of combined ZOL and meloxicam was not observed, combination therapy was well-tolerated and may be useful in the clinical management of bone-invasive feline OSCC.
口腔鳞状细胞癌(OSCC)在猫和人类中都很常见,并且会侵犯口腔骨骼。我们假设,环氧化酶(COX)-2抑制剂美洛昔康与双膦酸盐唑来膦酸(ZOL)联合使用,会抑制小鼠猫OSCC异种移植瘤的肿瘤生长、骨溶解和侵袭。人和猫的OSCC细胞系表达COX-1和COX-2,并且SCCF2细胞在骨条件培养基作用下COX-2 mRNA表达增加。将表达荧光素酶的猫SCCF2Luc细胞注射到上颌牙龈下方,小鼠分别接受每周两次0.1 mg kg⁻¹的ZOL、每日0.3 mg kg⁻¹的美洛昔康、ZOL与美洛昔康联合治疗或赋形剂处理。ZOL抑制肿瘤-骨界面处破骨细胞的骨吸收。在减少异种移植瘤生长方面,美洛昔康比ZOL更有效,但不影响破骨细胞的骨吸收。虽然未观察到ZOL与美洛昔康联合使用的协同效应,但联合治疗耐受性良好,可能对骨侵袭性猫OSCC的临床管理有用。