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HER-2 RNA interference improves sensitivity of breast cancer cells to chemotherapy in vitroand in vivo
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Abstract:
Objective: To observe the sensitivities of breast cancer cells and its implanted tumors to chemotherapeutic drug epirubicin after downregulation of HER2 expression by RNA interference (RNAi). Methods: HER2siRNApU6 vector containing HER2 RNAi was constructed and was used to transfect HER2 positive breast cancer cell line SKBR3. The expression of HER2 mRNA and protein were analyzed by RTPCR and Western blotting, respectively. Transfected SKBR3 cells were treated with different concentrations of epirubicin; the growth of SKBR3 cells and IC50 of epirubicin were observed by MTT. SKBR3 cells were injected into nude mouse to establish breast cancer model; the sensitivity of mouse model to epirubicin was observed after HER2shRNApU6 treatment. Results: Expression of HER2 mRNA and HER2 protein were downregulated in SKBR3 cells after transfection with HER2shRNApU6. Furthermore, the proliferation of SKBR3 cells transfected with HER2shRNApU6 was significantly decreased compared with mock tansfected group（P<0.05）. Chemosensitivity of SKBR3 cells to epirubicin was enhanced after treatment with HER2shRNApU6, with the IC50 values of HER2shRNApU6, mock, and negative tansfected group being 0.25, 3.46 and 3.69 μg/μl, respectively. The tumor weight was significantly lower in HER2shRNApU6 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: HER2 RNAi obviously inhibits the expression of HER2 mRNA and HER2 protein in SKBR3 breast cancer cells, thus increases their sensitivities to epirubicin in vitro and in vivo.
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Project Supported:
Supported by the National Natural Science Foundation of China（No.30801118）and the Natural Science Foundation of Zhejiang Province（No.Y207301）
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