紫杉醇联合曲妥珠单抗对人乳腺癌SKBR-3细胞移植裸鼠的治疗作用

Therapeutic efficacy of paclitaxel plus trastuzumab chemotherapy in nude mice transplanted with human breast cancer SKBR-3 cells

目的:观察紫杉醇联合曲妥珠单抗对人乳腺癌SKBR-3细胞移植裸鼠的治疗效果以及对瘤组织局部凋亡诱导因子程序性细胞死亡蛋白5(PDCD5)与凋亡抑制因子X-连锁凋亡抑制蛋白(XIAP)表达的影响。方法:用高表达Her-2的人乳腺癌SKBR-3细胞制备裸鼠皮下移植瘤模型,成瘤后,将荷瘤小鼠随机分组分别给予紫杉醇联合曲妥珠单抗(联合治疗组)、紫杉醇单药(紫杉醇组)、曲妥珠单抗单药(曲妥珠单抗组)、生理盐水(对照组)治疗。每周用药1次,6次后处死小鼠,取移植瘤称重后,分别用qPCR与Western bolt检测瘤组织PDCD5和XIAP基因与表达。结果:与对照组比较,各治疗组移植瘤质量均明显减小,瘤组织PDCD5mRNA与蛋白表达量均明显升高,XIAPmRNA与蛋白表达量均明显降低,且联合治疗组以上变化较2个单药组更为明显(均P<0.05)。单药组间比较,紫杉醇组降低XIAPmRNA与蛋白表达的作用强于曲妥珠单抗单组(均P<0.05),其他指标无统计学差异(均P>0.05)。结论:紫杉醇联合曲妥珠单抗化疗能有效抑制Her-2阳性乳腺癌移植瘤在裸鼠体内的生长,其作用可能与促进肿瘤PDCD5表达、同时降低XIAP表达有关。

Objective： To observe the therapeutic effect of paclitaxel plus trastuzumab chemotherapy on nude mice transplanted with human breast cancer SKBR-3 cells and its influence on the expressions of apoptosis-inducing factor programmed cell death 5 （PDCD5） and anti-apoptosis factor X-linked inhibitor of apoptosis protein （XIAP） in the tumor.Methods： The subcutaneous xenograft model in nude mice was established by using Her-2-overexpression human breast cancer SKBR-3 cells. After tumor formation, the mice were randomly grouped and treated with paclitaxel plus trastuzumab （combined treatment group）, paclitaxel alone （paclitaxel group）, trastuzumab alone （trastuzumab group）, and normal saline （control group）, respectively. The drugs were administered once weekly and after 6 times of administration, the mice were sacrificed, their tumors were harvested and weighed, and the gene and protein expressions of PDCD5 and XIAP in the tumors were determined by qPCR and Western blot analysis respectively.Results： In each treatment group compared with control group, the tumor weight was significantly reduced, the relative expression levels of both PDCD5 mRNA and protein were significantly increased, and the relative expression levels of both XIAP mRNA and protein were significantly decreased, moreover, all above changes were more evident in combined treatment group than those in either single drug treatment group （all P〈0.05）. Comparison between the two single drug treatment groups showed that the reducing effects of XIAP mRNA and protein were greater in paclitaxel group than those in trastuzumab group （both P〈0.05）, but no significant difference was noted in other parameters （all P〉0.05）.Conclusion： Paclitaxel plus trastuzumab chemotherapy can effectively inhibit the growth of Her-2-positive human breast cancer in nude mice, and this action may be associated with its up-regulating PDCD5 expression and meanwhile down-regulating XIAP expression.