目的: 观察RNA干扰（RNAi）下调HER2受体后乳腺癌细胞及其移植肿瘤对化疗药物表柔比星（epirubicin，EPI）敏感性的变化。方法: 构建能够表达HER2 siRNA 的质粒载体HER2shRNApU6,转染HER2 阳性的乳腺癌细胞SKBR3， RTPCR 与Western blotting 检测SKBR3细胞HER2 mRNA 与蛋白的表达。受转染细胞与不同浓度的化疗药物表柔比星共培养，MTT法检测细胞增殖活性及药物IC50；构建裸鼠乳腺癌模型，观察经HER2shRNApU6治疗后，肿瘤对化疗的敏感性。结果: SKBR3 细胞转染HER2shRNApU6后，HER2 mRNA及蛋白表达出现明显下调，细胞增殖活性出现明显下降（P<0.05），治疗组肿瘤细胞对表柔比星的化疗敏感性IC50为0.25 μg/μl，而阴性对照及空白对照分别为3.46 μg/μl和3.69 μg/μl。裸鼠移植肿瘤模型中，治疗组肿瘤重量明显低于空白对照和阴性对照\[（2.17±0.58） vs (3.13±0.38)、（3.21±0.89）g\]。结论: 〗HER2的RNA干扰显著抑制乳腺癌SKBR3细胞mRNA和蛋白表达，从而明显提高肿瘤细胞及其种植瘤对表柔比星的敏感性。

Objective: To observe the sensitivities of breast cancer cells and its implanted tumors to chemotherapeutic drug epirubicin after downregulation of HER2 expression by RNA interference (RNAi). Methods: HER2siRNApU6 vector containing HER2 RNAi was constructed and was used to transfect HER2 positive breast cancer cell line SKBR3. The expression of HER2 mRNA and protein were analyzed by RTPCR and Western blotting, respectively. Transfected SKBR3 cells were treated with different concentrations of epirubicin; the growth of SKBR3 cells and IC50 of epirubicin were observed by MTT. SKBR3 cells were injected into nude mouse to establish breast cancer model; the sensitivity of mouse model to epirubicin was observed after HER2shRNApU6 treatment. Results: Expression of HER2 mRNA and HER2 protein were downregulated in SKBR3 cells after transfection with HER2shRNApU6. Furthermore, the proliferation of SKBR3 cells transfected with HER2shRNApU6 was significantly decreased compared with mock tansfected group（P<0.05）. Chemosensitivity of SKBR3 cells to epirubicin was enhanced after treatment with HER2shRNApU6, with the IC50 values of HER2shRNApU6, mock, and negative tansfected group being 0.25, 3.46 and 3.69 μg/μl, respectively. The tumor weight was significantly lower in HER2shRNApU6 group than those in the mock and negative control group \[（2.17±0.58）vs (3.13±0.38),（3.21±0.89）g\]. Conclusion: HER2 RNAi obviously inhibits the expression of HER2 mRNA and HER2 protein in SKBR3 breast cancer cells, thus increases their sensitivities to epirubicin in vitro and in vivo.

国家自然科学基金资助项目（No.30801118）；浙江省自然科学基金资助项目（No.Y207301）