Sakaguchi Y, Maehara Y, Baba H, Kusumoto T, Sugimachi K, Newman R A
Cancer Center Kyushu University Hospital, Japan.
Cancer Res. 1992 Jun 15;52(12):3306-9.
The combined effects of flavone acetic acid (FAA), a synthetic flavonoid, and hyperthermia on B16 melanoma cells were investigated. In vitro, FAA alone at concentrations below 100 micrograms/ml was not cytotoxic with a 60-min exposure at 37 degrees C. Hyperthermia at 43 degrees C for 60 min enhanced the cytotoxicity of FAA only at concentrations over 100 micrograms/ml. Inhibition of the growth of B16 melanoma solid tumor by FAA and/or hyperthermia was examined in vivo. FAA (100-200 mg/kg) inhibited tumor growth in a dose-dependent manner. The combined treatment of FAA (200 mg/kg) and hyperthermia (43 degrees C, 15 min) significantly inhibited tumor growth compared to a treatment of FAA or hyperthermia alone. The maximum antitumor effect of FAA combined with hperthermia was obtained when FAA was administered 2 or 4 h before heat. The significantly increased cytotoxicity of FAA combined with hyperthermia seems to relate to specific decreases in tumor blood flow, a reduction in tumor pH, and an increased tumor temperature, without altering pH in the normal tissues. This combined treatment of FAA and hyperthermia warrants further study for treating subjects with solid tumors.
研究了合成黄酮类化合物黄酮醋酸（FAA）与热疗对B16黑色素瘤细胞的联合作用。在体外，浓度低于100微克/毫升的FAA单独作用时，在37℃下暴露60分钟没有细胞毒性。43℃热疗60分钟仅在FAA浓度超过100微克/毫升时增强其细胞毒性。在体内检测了FAA和/或热疗对B16黑色素瘤实体瘤生长的抑制作用。FAA（100 - 200毫克/千克）以剂量依赖方式抑制肿瘤生长。与单独使用FAA或热疗相比，FAA（200毫克/千克）与热疗（43℃，15分钟）联合治疗显著抑制肿瘤生长。当在热疗前2或4小时给予FAA时，FAA与热疗联合的抗肿瘤效果最佳。FAA与热疗联合时细胞毒性显著增加似乎与肿瘤血流的特异性减少、肿瘤pH值降低以及肿瘤温度升高有关，而正常组织的pH值未改变。FAA与热疗的这种联合治疗值得进一步研究用于实体瘤患者的治疗。
