title: Plasmid-based STAT3-siRNA efficiently inhibits breast tumor growth and metastasis in mice.
abstract: Signal transducer and activator of transcription 3 (STAT3) plays an important role in the tumor formation and metastasis. In this study, short hairpin RNA targeting STAT3 was cloned into pGenesil-2 plasmid vector and the effects of STAT3 silencing in 4T1 breast cancer cells were analyzed both in vitro and in vivo. Forty-eight hours after transfecting with pSi-STAT3, the expression level of STAT3, the upstream regulator and downstream targets were measured using Western blot. Moreover, the effects of pSi-STAT3 on migration and invasion in 4T1 cells were tested using wound-healing and tube formation assay. Furthermore, 4T1 subcutaneous mice model was used to evaluate the effects of pSi-STAT3 on tumor growth and metastasis. Proliferation, apoptosis, angiogenesis in tumor tissues and lung metastases were measured by PCNA, TUNEL, and CD31 immunostaining, respectively. Our results indicated that siRNA targeting STAT3 could significantly silence STAT3 expression in 4T1 breast cancer cells and result in inhibition of 4T1 breast cells migration and HUVECs tube formation. In vivo, pSi-STAT3 delayed tumor growth (pknockdown of STAT3 by plasmid-based siRNA might be a potential therapy against breast cancer.
authors: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, The People's Republic of China.
authors: L
authors: L
authors: Dai
authors: L
authors: L
authors: Cheng
authors: X
authors: X
authors: Zhang
authors: Q
authors: Q
authors: Jiang
authors: S
authors: S
authors: Zhang
authors: S
authors: S
authors: Wang
authors: Y
authors: Y
authors: Li
authors: X
authors: X
authors: Chen
authors: T
authors: T
authors: DU
authors: Y
authors: Y
authors: Yang
authors: H
authors: H
authors: Tian
authors: P
authors: P
authors: Fan
authors: N
authors: N
authors: Yan
authors: L
authors: L
authors: Dai
authors: Y
authors: Y
authors: Wei
authors: H
authors: H
authors: Deng
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D034741:RNA, Small Interfering / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D014945:Wound Healing
chemical_list: D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse