KU004抑制人源乳腺癌BT474裸鼠异种移植模型肿瘤生长的作用

KU004 inhibits tumor growth in human breast cancer BT474 nude mouse xenograft model

目的探讨KU004对人源乳腺癌BT474裸鼠异种移植模型肿瘤的抑制作用。方法对60只雌性BALB/c裸鼠接种人源乳腺癌BT474细胞,将肿瘤生长至100～160 mm^3的40只裸鼠随机分为模型组(0.5%羟丙基甲基纤维素溶液灌胃)、拉帕替尼组(80 mg/kg拉帕替尼灌胃)、KU004高剂量组(120 mg/kg KU004灌胃)、KU004中剂量组(80 mg/kg KU004灌胃)、KU004低剂量组(40 mg/kg KU004灌胃),每组8只,每天灌胃1次,连续灌胃21 d。分别于给药前以及给药后1 d、4 d、7 d、11 d、14 d、17 d、21 d测量各组裸鼠体重及肿瘤体积,计算相对肿瘤增殖率(T/C)和肿瘤抑制率(inhibition rate,IR)。结果成功建立人源乳腺癌BT474裸鼠异种移植模型。拉帕替尼组、KU004高剂量组、KU004中剂量组、KU004低剂量组裸鼠体重随给药时间延长变化不大,与模型组比较差异均无统计学意义(P>0.05)。给药期间各给药组TV、RTV均低于与模型组(P<0.01),其中拉帕替尼组与KU004中剂量组TV、RTV比较差异无统计学意义(P>0.05)。拉帕替尼组、KU004高剂量组、KU004中剂量组和KU004低剂量组T/C随给药时间延长逐渐降低,至给药后21 d T/C分别为15.6%、6.9%、11.4%和32.7%,IR分别为85.0%、95.0%、91.0%和67.0%。结论不同剂量KU004均可对人源乳腺癌BT474裸鼠异种移植模型肿瘤生长产生抑制作用,且裸鼠耐受性良好。

Objective To investigate the inhibitory effect of KU004 in human breast cancer BT474 nude mouse xenograft model.Methods 60 female BALB/c nude mice were inoculated with human breast cancer BT474 cells,and 40 with tumor growth to 100-160 mm^3 were randomly divided into 5 groups（n=8）;they were gavaged with 40,80,or 120 mg/kg KU004;80 mg/kg lapatinib or 0.5%hydroxypropyl methylcellulose solution respectively,once a day for 21 days. Before and 1,4,7,11,14,17,21 days after the administration,tumor volume and weight were measured in all 5 groups,and relative tumor growth rate（T/C）and tumor inhibition rate（IR）were calculated. Results Human breast cancer BT474 nude mouse xenograft model was successfully established. The tumor weight in lapatinib,high-,medium-and low-dose KU004 groups had little change,but there was no significant difference when compared with the model group（P0.05）. The TV and RTV of each drug-administered group were significantly lower than that in the model group（P0.01）,while there was no significant difference between the lapatinib group and the KU004 medium-dose group（P0.05）. The T/C in lapatinib group,high-,mid-,and low-dose KU004 group gradually decreased,and T/C was 15.6%,6.9%,11.4%,and 32.7% at 21 days,and IR was 85.0%,95.0%,91.0%,and 67.0%,respectively. Conclusions KU004 in high-,mid-,and low dose can inhibit the tumor growth of human breast cancer BT474 xenograft model,and the nude mice can tolerate well.