CONCLUSION: Our results indicate that siRNA E6 and/or E7 may have potential as a gene-specific therapy for human papillomavirus (HPV) type 16 (HPV16)-related squamous cell carcinoma of the head and neck (HNSCC). OBJECTIVES: To evaluate the effectiveness of siRNA targeting E6 and/or E7 on the in vitro and in vivo growth suppression of HPV16-related HNSCC. METHODS: HPV16-related HNSCC (UM-SCC47) cell lines were used for the present study. Expression of HPV viral oncogenes E6 and/or E7 and their cellular targets, p53 and pRb, was evaluated by real-time PCR, Western blotting, and immunofluorescence staining. To study the effect of siRNA on tumor growth in vivo, we developed animal models. Representative tumors harvested from each group were processed for apoptosis analyses (TUNEL assay) and immunofluorescence staining for p53 and pRb. RESULTS: E6 and E7 oncogenes of HPV16 were down-regulated by E6 and/or E7 targeting siRNAs, respectively. The expression of p53 and pRb proteins in both the E6 siRNA group and E7 siRNA group was up-regulated compared with those of control groups. The cellular proliferation and apoptosis indexes of E6 and/or E7 siRNA groups were higher than those of controls. In vivo studies showed significant inhibitory effect of E6 and/or E7 siRNA compared with those of control groups, which was consistent with in vitro studies.
CONCLUSION: Our results indicate that siRNA E6 and/or E7 may have potential as a gene-specific therapy for human papillomavirus (HPV) type 16 (HPV16)-related squamous cell carcinoma of the head and neck (HNSCC). OBJECTIVES: To evaluate the effectiveness of siRNA targeting E6 and/or E7 on the in vitro and in vivo growth suppression of HPV16-related HNSCC. METHODS:HPV16-related HNSCC (UM-SCC47) cell lines were used for the present study. Expression of HPV viral oncogenes E6 and/or E7 and their cellular targets, p53 and pRb, was evaluated by real-time PCR, Western blotting, and immunofluorescence staining. To study the effect of siRNA on tumor growth in vivo, we developed animal models. Representative tumors harvested from each group were processed for apoptosis analyses (TUNEL assay) and immunofluorescence staining for p53 and pRb. RESULTS: E6 and E7 oncogenes of HPV16 were down-regulated by E6 and/or E7 targeting siRNAs, respectively. The expression of p53 and pRb proteins in both the E6 siRNA group and E7 siRNA group was up-regulated compared with those of control groups. The cellular proliferation and apoptosis indexes of E6 and/or E7 siRNA groups were higher than those of controls. In vivo studies showed significant inhibitory effect of E6 and/or E7 siRNA compared with those of control groups, which was consistent with in vitro studies.
Authors: Ning Jiang; Dongsheng Wang; Zhongliang Hu; Hyung Ju C Shin; Guoqing Qian; Mohammad Aminur Rahman; Hongzheng Zhang; A R M Ruhul Amin; Sreenivas Nannapaneni; Xiaojing Wang; Zhengjia Chen; Gabriela Garcia; Gavin MacBeath; Dong M Shin; Fadlo R Khuri; Jun Ma; Zhuo G Chen; Nabil F Saba Journal: Mol Cancer Ther Date: 2014-04-18 Impact factor: 6.261
Authors: Toni M Brand; Stefan Hartmann; Neil E Bhola; Hua Li; Yan Zeng; Rachel A O'Keefe; Max V Ranall; Sourav Bandyopadhyay; Margaret Soucheray; Nevan J Krogan; Carolyn Kemp; Umamaheswar Duvvuri; Theresa LaVallee; Daniel E Johnson; Michelle A Ozbun; Julie E Bauman; Jennifer R Grandis Journal: Cancer Res Date: 2018-02-12 Impact factor: 13.312