Scioscia K A, Snyderman C H, D'Amico F, Comsa S, Rueger R, Light B
Department of Otolaryngology, University of Pittsburgh Medical Center, Eye & Ear Institute, Suite 500, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA.
Head Neck. 2000 Mar;22(2):149-55. doi: 10.1002/(sici)1097-0347(200003)22:2<149::aid-hed6>3.0.co;2-t.
A murine model (C3H mice) of squamous cell carcinoma (SCCVII) has been used to investigate the role of arachidonic acid (AA) metabolites in head and neck cancer. Inhibition of tumor growth by cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors of AA metabolism has been associated with changes in levels of AA metabolites in tumor tissues and inflammatory cell infiltrates. To characterize this model further, the effects of exogenous AA metabolites on tumor growth in vitro and in vivo were investigated.
Following subcutaneous inoculation with SCCVII tumor cells, control (16 mice) and treatment (24 mice) groups were injected with peritumoral vehicle or AA metabolite. Peritumoral injections of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and 12-hydroxyeicosatetraenoic acid (12-HETE) were performed for 16-21 days, and final excised tumor weights were measured. In vitro production of PGE2 and LTB4 was assayed in 2-5 day cultures of SCCVII. Exogenous PGE2 effects on tumor cell growth was assessed with the MTT assay in vitro.
Tumor growth was significantly inhibited (p =.03) following peritumoral injection of PGE2. Final tumor weights were not affected by LTB4 or 12-HETE. Tumor inhibition by PGE2 was associated with increased tumor tissue levels of LTB4 (p =.04). In vitro, SCCVII produced minimal amounts of PGE2 and LTB4, and PGE2 had minimal effect on growth.
In this model, tumor inhibition by exogenous PGE2 is primarily mediated by affecting host-tumor interactions, although there may be some direct effect on tumor cells. Changes in tumor tissue levels of LTB4 following peritumoral PGE2 administration may be attributable to negative feedback inhibition of the COX pathway with shunting into the LOX pathway. SCCVII cells are probably not a significant source of prostaglandins and leukotrienes in vivo. These data provide insight into the mechanism of action of inhibitors of AA metabolism on tumor growth.
一种鳞状细胞癌（SCCVII）的小鼠模型（C3H小鼠）已被用于研究花生四烯酸（AA）代谢产物在头颈癌中的作用。AA代谢的环氧化酶（COX）和脂氧合酶（LOX）抑制剂对肿瘤生长的抑制作用与肿瘤组织和炎性细胞浸润中AA代谢产物水平的变化有关。为了进一步表征该模型，研究了外源性AA代谢产物对体外和体内肿瘤生长的影响。
在皮下接种SCCVII肿瘤细胞后，对照组（16只小鼠）和治疗组（24只小鼠）分别注射瘤周载体或AA代谢产物。瘤周注射前列腺素E2（PGE2）、白三烯B4（LTB4）和12-羟基二十碳四烯酸（12-HETE）持续16 - 21天，并测量最终切除肿瘤的重量。在SCCVII的2 - 5天培养物中检测PGE2和LTB4的体外产生。体外通过MTT法评估外源性PGE2对肿瘤细胞生长的影响。
瘤周注射PGE2后肿瘤生长受到显著抑制（p = 0.03）。最终肿瘤重量不受LTB4或12-HETE影响。PGE2对肿瘤的抑制作用与肿瘤组织中LTB4水平升高有关（p = 0.04）。在体外，SCCVII产生极少量的PGE2和LTB4，且PGE2对生长的影响极小。
在该模型中，外源性PGE2对肿瘤的抑制作用主要通过影响宿主 - 肿瘤相互作用介导，尽管可能对肿瘤细胞有一些直接作用。瘤周给予PGE2后肿瘤组织中LTB4水平的变化可能归因于COX途径的负反馈抑制并转向LOX途径。SCCVII细胞在体内可能不是前列腺素和白三烯的重要来源。这些数据为AA代谢抑制剂对肿瘤生长的作用机制提供了见解。
