Down-regulating HIF-1α by lentivirus-mediated shRNA for therapy of triple negative breast cancer.
Hypoxia is associated with poor response to treatment in various cancers. Hypoxia inducible factor 1 (HIF-1) is a major transcription factor that mediates adaptation of cancer cells to a hypoxic environment and regulates many genes that are involved in key cellular functions, including cell immortalization, stem cell maintenance, autocrine growth/survival, angiogenesis, invasion/metastasis, and resistance to chemotherapy. HIF-1α has been considered as an attractive therapeutic target for cancer treatment, but there is limited success in this research field. In the present study, we designed a recombinant lentivirus containing HIF-1α siRNA, developed stably transfected cell lines, and tested the anticancer effects of the siRNA on cancer cells in vitro and in vivo. Our results indicated that the stable downregulation of HIF-1α reversed chemoresistance, inhibited proliferation, migration and invasion of cancer cells, and slowed down the tumor growth in breast cancer xenograft models. In conclusion, the recombinant lentivirus containing HIF-1α siRNA provides a new avenue for developing novel therapy for triple negative breast cancer.
['Li|Shuang|S|', 'Wei|Qingzhu|Q|', 'Li|Qin|Q|', 'Zhang|Bin|B|', 'Xiao|Qiang|Q|']
D000818:Animals D017209:Apoptosis D059447:Cell Cycle Checkpoints D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D004195:Disease Models, Animal D005260:Female D055785:Gene Knockdown Techniques D015316:Genetic Therapy D005822:Genetic Vectors D006801:Humans D051795:Hypoxia-Inducible Factor 1, alpha Subunit D016086:Lentivirus D008297:Male D051379:Mice D034622:RNA Interference D034741:RNA, Small Interfering D014161:Transduction, Genetic D064726:Triple Negative Breast Neoplasms D023041:Xenograft Model Antitumor Assays
HIF-1α triple negative breast cancer recombinant lentivirus stably transfected cell lines BCSCs, breast cancer stem cells EGFR, epidermal growth factor receptor HIF-1α, hypoxia inducible factor-1α MDR, multidrug resistance PARP, poly ADP ribose polymerase PI3K, phosphatidylinositol 3-kinase TNBC, triple negative breast cancer VEGF, va apoptosis gene therapy siRNA therapy