Watts M E, Murray J C, Smith K A, Woodcock M
Gray Laboratory of the Cancer Research Campaign, Mount Vernon Hospital, Northwood, Middlesex, U.K.
Int J Radiat Oncol Biol Phys. 1992;22(3):431-5. doi: 10.1016/0360-3016(92)90847-b.
Flavone acetic acid (FAA) causes significant regression of larger established tumors in murine systems in vivo, but is only slightly toxic in vitro. This in vivo effect is thought to be indirect, or immunological, rather than a direct cytotoxic effect on tumor cells. Using the WHFIB fibrosarcoma, which grows both in vivo and in vitro, and the murine endothelial cell line B10, we have studied the effect of FAA on the survival of tumor and endothelial cells in vitro. The times taken for 1 mg ml-1 FAA to reduce survival to 0.1 surviving fraction were 63 hr for B10 and greater than 85 hr for WHFIB in vitro. WHFIB tumors in vivo were more sensitive than tumor cells in vitro, a single dose of 150 mg kg-1 FAA inducing a tumor growth delay of 10 days at treatment size + 2 mm. As FAA is more toxic to tumor-bearing animals than to those which are non-tumor bearing the effect of tumor conditioned medium on the cytotoxicity of FAA toward B10 cells was studied; no enhanced effect was seen. As FAA is only weakly cytotoxic in vitro to endothelial cells, and even less so to tumor cells, sublethal effects of FAA on endothelial cell function in vitro were studied. The permeability of monolayers of human unbilical vein endothelial cells (HUVEC) in vitro is transiently increased by FAA. Also, procoagulant activity of HUVEC is induced by FAA and this activity is further enhanced in the presence of a factor isolated from Meth-A tumor cells.
黄酮醋酸（FAA）可使小鼠体内已形成的较大肿瘤显著消退，但在体外仅有轻微毒性。这种体内效应被认为是间接的，即免疫性的，而非对肿瘤细胞的直接细胞毒性作用。利用在体内和体外均能生长的WHFIB纤维肉瘤以及小鼠内皮细胞系B10，我们研究了FAA对体外肿瘤细胞和内皮细胞存活的影响。在体外，1 mg/ml的FAA使B10细胞存活率降至0.1存活分数所需时间为63小时，而使WHFIB细胞降至该存活分数所需时间超过85小时。体内的WHFIB肿瘤比体外肿瘤细胞更敏感，单剂量150 mg/kg的FAA在肿瘤大小为治疗时大小 + 2 mm时可使肿瘤生长延迟10天。由于FAA对荷瘤动物的毒性比对非荷瘤动物更大，因此研究了肿瘤条件培养基对FAA对B10细胞细胞毒性的影响；未观察到增强效应。由于FAA在体外对内皮细胞的细胞毒性较弱，对肿瘤细胞的细胞毒性更弱，因此研究了FAA对体外内皮细胞功能的亚致死效应。FAA可使体外人脐静脉内皮细胞（HUVEC）单层的通透性短暂增加。此外，FAA可诱导HUVEC的促凝活性，并且在存在从Meth-A肿瘤细胞分离出的一种因子时，这种活性会进一步增强。
