title: RNA interference-mediated downregulation of hypoxia-inducible factor-1α inhibits angiogenesis and survival of oral squamous cell carcinoma in vitro and in vivo.
abstract: Hypoxia-inducible factor-α (HIF-1α) is the key transcription factor involved in the adaptive response to hypoxia. It has been established that HIF-1α is overexpressed in various human cancers, including oral squamous cell carcinoma (OSCC), and orchestrates a wide spectrum of many key cancer molecular pathways involved in diverse tumor progression. In this study, RNA interference (RNAi) was introduced to downregulate the expression of HIF-1α in OSCC in vitro and in vivo. The mRNA and protein expression levels of HIF-1α and vascular epidermal growth factor were detected by quantitative real-time reverse transcription-PCR, western blot, and immunohistochemistry, and cell proliferation activity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tumor growth, microvascular density, apoptosis, and the expression of proliferation-related gene Ki-67 in tumor xenografts were evaluated. Our data demonstrated that small interfering RNA targeting HIF-1α significantly inhibited the mRNA and protein expression levels of HIF-1α and vascular epidermal growth factor. In addition, marked suppression of tumor cell prolifeation and xenograft growth, significant microvascular density suppression, reduced expression of Ki-67, and increased cell apoptosis were observed. These findings suggest that RNAi targeting HIF-1α could effectively inhibit the progression of OSCC. Thus, it may be used as a potent and specific therapy for oral cancer, especially in inhibiting and preventing cancer cell angiogenesis and survival.
authors: Department of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Diseases, Sichuan University, No. 14 Sec. 3 Renminnan Road, Chengdu, Sichuan, PR China.
authors: Hao
authors: H
authors: Zhou
authors: Wei
authors: W
authors: Fei
authors: Yun
authors: Y
authors: Bai
authors: Songsong
authors: S
authors: Zhu
authors: En
authors: E
authors: Luo
authors: Kai
authors: K
authors: Chen
authors: Jing
authors: J
authors: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism* / Q000517:prevention & control; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011897:Random Allocation
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering