title: Stable RNA interference of ErbB-2 gene synergistic with epirubicin suppresses breast cancer growth in vitro and in vivo.
abstract: Overexpression of human epidermal growth factor receptor-2 (Her2, ErbB-2) contributes to the progression and metastasis of breast cancer, implying that Her2 gene is a suitable target of RNA interference (RNAi) for breast cancer therapy. Here, we employed plasmid-mediated expression of 2 different Her2-shRNAs (pU6-Her2shRNAs) efficiently silenced the target gene expression on Her2 expressing SKBR-3 breast cancer cells in both mRNA and protein levels. Consequently, pU6-Her2shRNA increased apoptosis and reduced proliferation of SKBR-3 cells assayed by TUNEL and MTT, respectively. In vivo, intra-tumor injection of pU6-Her2shRNA inhibited the growth of SKBR-3 tumors inoculated subcutaneously in nude mice. Furthermore, pU6-Her2shRNA synergized the tumor suppression effect of epirubicin to SKBR-3 cells in vitro and implanted subcutaneously in nude mice. Therefore, we concluded that stable silencing of Her2 gene expression with plasmid expressing shRNA may hold great promise as a novel therapy for Her2 expressing breast cancers alone or in combination with anthracycline chemotherapy.
authors.affiliation: Department of Breast Surgery, Sun-Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou 510120, People's Republic of China.
authors.forename: Xiaoqu
authors.initials: X
authors.lastname: Hu
authors.forename: Fengxi
authors.initials: F
authors.lastname: Su
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Weijuan
authors.initials: W
authors.lastname: Jia
authors.forename: Chang
authors.initials: C
authors.lastname: Gong
authors.forename: Fengyan
authors.initials: F
authors.lastname: Yu
authors.forename: Jujiang
authors.initials: J
authors.lastname: Guo
authors.forename: Erwei
authors.initials: E
authors.lastname: Song
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D015251:Epirubicin / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D015251:Epirubicin; D018719:Erb-b2 Receptor Tyrosine Kinases