Cliffe S, Taylor M L, Rutland M, Baguley B C, Hill R P, Wilson W R
Department of Pathology, University of Auckland School of Medicine, New Zealand.
Int J Radiat Oncol Biol Phys. 1994 May 15;29(2):373-7. doi: 10.1016/0360-3016(94)90292-5.
To determine whether 5,6-dimethylxanthenone acetic acid (DMXAA), a potent analogue of flavone acetic acid (FAA) inhibits blood flow in mouse mammary tumors, and to assess whether DMXAA enhances the antitumor effects of Tirapazamine (SR 4233) and the novel bioreductive drug SN 23862 (a dinitrobenbenzene mustard).
MDAH-MCa-4 mouse mammary tumors were grown i.m. in the leg of C3H/HeN mice. Tumor blood flow was assessed by the pertechnetate clearance method and subsequent growth delay was determined in the same tumors.
Administration of DMXAA (65-70 mumol/kg) resulted in inhibition of tumor blood flow to approximately 25% of control values, with no recovery observed up to 36 h post-treatment. Combination of DMXAA with SR 4233 provided a significant increase in tumor growth inhibition relative to either drug alone. In this effect, DMXAA was qualitatively similar to FAA, but was approximately 10 x more potent. The interaction between DMXAA (65 mumol/kg) and SR 4233 (200 mumol/kg) was maximal with SR 4233 given between 15 min before and 60 min after DMXAA. For SN 23862, a similar enhanced growth delay was observed in combination with DMXAA, with no obvious time dependence between 15 min before and 4 h after DMXAA. When mean values for groups treated with SR 4233 (200 mumole/kg) alone and in combination with DMXAA (65-90 mumole/kg) were compared, a correlation was observed between tumor blood flow inhibition and subsequent growth delay.
DMXAA is a potent inhibitor of blood flow in MDAH-MCa-4 tumors. Combination of this vasoactive drug with bioreductive agents leads to an enhanced antitumor effect. For SR 4233 and DMXAA, this enhanced effect may be predictable by measurement of tumor blood flow inhibition shortly after drug administration.
确定黄酮乙酸（FAA）的强效类似物5,6 - 二甲基呫吨酮乙酸（DMXAA）是否能抑制小鼠乳腺肿瘤的血流，并评估DMXAA是否能增强替拉扎明（SR 4233）和新型生物还原药物SN 23862（一种二硝基苯芥子气）的抗肿瘤作用。
将MDAH - MCa - 4小鼠乳腺肿瘤接种于C3H/HeN小鼠腿部的肌肉中。通过高锝酸盐清除法评估肿瘤血流，并测定同一肿瘤随后的生长延迟情况。
给予DMXAA（65 - 70μmol/kg）可使肿瘤血流抑制至对照值的约25%，在治疗后36小时内未观察到恢复情况。DMXAA与SR 4233联合使用相对于单独使用任何一种药物，肿瘤生长抑制作用显著增强。在这种作用中，DMXAA在性质上与FAA相似，但效力约强10倍。当在DMXAA给药前15分钟至给药后60分钟之间给予SR 4233时，DMXAA（65μmol/kg）与SR 4233（200μmol/kg）之间的相互作用最大。对于SN 23862，与DMXAA联合使用时观察到类似的生长延迟增强，在DMXAA给药前15分钟至给药后4小时之间无明显时间依赖性。当比较单独使用SR 4233（200μmol/kg）和与DMXAA（65 - 90μmol/kg）联合使用的组的平均值时，观察到肿瘤血流抑制与随后的生长延迟之间存在相关性。
DMXAA是MDAH - MCa - 4肿瘤血流的强效抑制剂。这种血管活性药物与生物还原剂联合使用可增强抗肿瘤作用。对于SR 4233和DMXAA，给药后不久通过测量肿瘤血流抑制情况可能可预测这种增强作用。
