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.
a Graduate School of Southern Medical University ; Guangzhou , China.
Shuang
S
Li
Qingzhu
Q
Wei
Qin
Q
Li
Bin
B
Zhang
Qiang
Q
Xiao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D014161:Transduction, Genetic; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D023041:Xenograft Model Antitumor Assays
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering
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; HIF-1α; apoptosis; gene therapy; recombinant lentivirus; siRNA therapy; stably transfected cell lines; triple negative breast cancer