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目的探讨分子靶向药物甲磺酸伊马替尼与多烯紫杉醇联合对乳腺癌皮下移植瘤生长的影响。方法 ALB/c-nu裸鼠56只,制备人乳腺癌细胞株MCF-7裸鼠皮下移植瘤模型并随机分为8组,分别为高剂量紫杉醇(20 mg/kg)组(高剂量组)、中剂量紫杉醇(10 mg/kg)组(中剂量组)、低剂量紫杉醇(5 mg/kg)组(低剂量组)、甲磺酸伊马替尼组、高剂量紫杉醇与甲磺酸伊马替尼联合组(高剂量联合组)、中剂量紫杉醇与甲磺酸伊马替尼联合组(中剂量联合组)、低剂量紫杉醇与甲磺酸伊马替尼联合组(低剂量联合组)、生理盐水组,每组7只。从接种第3天开始给药,高、中、低剂量组分别于第1、7、14天腹腔注射20、10、5 mg/kg多烯紫杉醇;甲磺酸伊马替尼组给予甲磺酸伊马替尼100 mg/kg灌胃,1次/d;高、中、低剂量联合组分别于第1、7、14天腹腔注射20、10、5 mg/kg多烯紫杉醇,同时给予甲磺酸伊马替尼100 mg/kg灌胃,1次/d;生理盐水组腹腔注射生理盐水2 mL。比较8组裸鼠移植瘤生长情况;实验结束处死裸鼠,取瘤组织称质量,计算抑瘤率。结果高、中、低剂量组[(0.130 9±0.071 2)、(0.206 6±0.098 4)、(1.067 4±0.051 5)g],高、中、低剂量联合组[(0.090 2±0.0003 8)、(0.110 5±0.013 9)、(0.836 5±0.013 8)g]及甲磺酸伊马替尼组[(1.835 3±0.308 3)g]裸鼠移植瘤质量明显低于生理盐水组[(2.583 1±0.356 3)g](P<0.05),高、中、低剂量联合组裸鼠移植瘤质量分别低于高、中、低剂量组(P<0.05);高、中、低剂量联合组(99.85%、95.72%、67.62%),高、中、低剂量组(94.93%、92.00%、58.68%)及甲磺酸伊马替尼组抑瘤率(28.95%)明显低于生理盐水组(0)(P<0.05),高、中、低剂量组,高、中、低剂量联合组抑瘤率明显高于甲磺酸伊马替尼组(P<0.05),中、高剂量组及中、高剂量联合组抑瘤率分别高于低剂量组和低剂量联合组(p<0.05)。结论高、中、低剂量多烯紫杉醇与甲磺酸伊马替尼联合对人乳腺癌细胞株MCF-7裸鼠移植瘤增殖的抑制具有相加作用,甲磺酸伊马替尼能增强多烯紫杉醇的抑瘤作用,降低其使用的有效浓度。
Objective To investigate the effect of molecular targeted drug imatinib mesylate in combination with docetaxel on the growth of subcutaneous xenografted breast cancer. Methods Fifty-six nude mice were divided into 8 groups: high dose paclitaxel (20 mg / kg) group (high dose group), nude mice with ALB / c-nu nude mice , Middle dose paclitaxel (10 mg / kg) group (middle dose group), low dose paclitaxel (5 mg / kg) group (low dose group), imatinib mesylate group, high dose paclitaxel and methanesulfonic acid Low-dose paclitaxel combined with imatinib mesylate (low-dose combination group), mid-dose paclitaxel combined with imatinib mesylate group (medium dose combination group), low-dose paclitaxel combined with imatinib mesylate group ), Saline group, 7 rats in each group. From the third day after inoculation, the high, middle and low dose groups were injected intraperitoneally with docetaxel 20, 10 and 5 mg / kg on the 1st, 7th and 14th days, respectively. The Imatinib mesylate group was given mesotrione Administration of imatinib 100 mg / kg orally, once / d; high, medium and low dose combination group were injected intraperitoneally with docetaxel 20, 10, and 5 mg / kg on days 1, Imatinib mesylate 100 mg / kg intragastric administration, 1 / d; saline group, intraperitoneal injection of saline 2 mL. The growth of transplanted tumor in 8 groups was compared; the nude mice were sacrificed at the end of the experiment, the tumor tissue was weighed and the tumor inhibition rate was calculated. Results High, medium and low dose groups [(0.130 9 ± 0.071 2), (0.206 6 ± 0.098 4), (1.067 4 ± 0.051 5) g], high, medium and low dose groups [(0.090 2 ± 0.0003 8 ), (0.110 5 ± 0.013 9), (0.836 5 ± 0.013 8) g] and imatinib mesylate group [(1.835 3 ± 0.308 3) g] were significantly lower than those in saline group [ (2.583 ± 0.356 3) g] (P <0.05). The transplanted tumors in nude mice in high, medium and low dose groups were lower than those in high, medium and low dose groups (P <0.05) The tumor inhibition rate (94.95%, 92.00%, 58.68%) and imatinib mesylate group (28.95%) in the combination group were significantly lower than those in the physiological group (99.85%, 95.72%, 67.62% Saline group (0) (P <0.05). The tumor inhibition rates of high, medium and low dose groups were significantly higher than those of imatinib mesylate group (P <0.05) The tumor inhibition rates in the dose group and medium and high dose combination groups were higher than those in the low and low dose groups, respectively (p <0.05). Conclusions Combination of high, medium and low doses of docetaxel with imatinib mesylate can inhibit the proliferation of human breast cancer cell line MCF-7 in nude mice, and imatinib mesylate can enhance more Paclitaxel antitumor effect, reduce the effective concentration of its use.