表皮生长因子受体抑制剂AG1478对乳腺癌裸鼠移植瘤的生长影响

目的 观察表皮生长因子受体抑制剂AG1478和内分泌治疗联合应用对乳腺癌荷瘤裸鼠移植瘤生长的影响.方法 应用MCF-7乳腺癌细胞建立裸鼠动物模型,当肿瘤体积在100～200 mm3时,按肿瘤体积大小将裸鼠随机分成溶剂对照组、AG1478组、三苯氧胺(TAM)组、AG1478+TAM组,分别给予空白溶剂、AG1478腹腔注射、TAM灌胃、AG1478腹腔注射和TAM灌胃.同时给药6周,动态观察移植瘤生长,用药结束后2d处死裸鼠,取肿瘤称重、计算肿瘤体积(V=长径×短径2×π/6)、抑瘤率((V对照组-V实验组)/V对照组]×100%).结果 各组裸鼠体重和肿瘤体积在治疗前具有均衡性.用药期间,溶剂对照组肿瘤生长最快,AGl478组次之,TAM组肿瘤生长较缓慢,而AGl478+TAM组肿瘤有缩小趋势.用药结束后,各组的抑瘤率分别为AG1478组30.4%,TAM组62%,AG1478+TAM组84.8%,与对照组比较差异有统计学意义(P<0.05).结论 AG1478对乳腺癌裸鼠移植瘤具有抑制作用,也可以加强三苯氧胺的抑瘤效果,两者有明显协同作用.

Effect of epidermal growth factor receptor inhibitor AG1478 on growth of breast carcinoma xenografts in nude mice

Objective To observe the effect of epidermal growth factor receptor (EGFR) inhibitor AG1478 combined with endocrine therapy on growth of breast carcinoma xenografts in nude mice. Methods Breast carcinoma nud mice model was created by using MCF-7 breast cancer cells. The mice were divided into 4 groups when average volume of tumor was about 100-200 ram3 :control group, AG1478 group, tamoxifen (TAM) group, AG1478 + TAM group, separately receiving empty dissolvent, AG1478 i. p,TAM gastric gavage (G. G), AG1478 i. p and TAM G. G. During a treatment period of 6 weeks,growth of breast carcinoma xenografts was observed. The mice were sacrificed at 2nd day after the treatment. Tumor masses were removed and weighted. Tumor volume was determined by direct measurement with caliper and calculated. The tumor inhibition rate was calculated. Results The nud mice weight and tumor volume had been balanced, before treatment. Tumor masses in control group grew more rapidly than that in AG1478 group. The tumor in TAM group grew slowly. Tumor masses were reduced in AG1478 + TAM group. After the treatment, the tumor inhibition rate in AG1478 group, TAM group and AG1478 + TAM group was 30.4% ,62% and 84.8% ,respectively,significantly higher than in control group (P< 0.05). Conclusion AG1478 could inhibit the growth of breast cancer nud mice xenografts. It also could improve the anti-tumor effect of tamoxifen. AG1478 and TAM had synergic effects.