Adenovirus-mediated transfer of HPV 16 E6/E7 antisense RNA combined with cisplatin inhibits cellular growth and induces apoptosis in HPV-positive head and neck cancer cells
Autor: | Natsumi Uehara, Hiroki Saito, Junko Kitamoto, Mie Kubo, Kyoko Kosaka, Naoya Morishita, Ken-Ich Nibu, Eri Takata, Yasutaka Kojima, Naoki Otsuki, Toshiro Shirakawa |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Cancer Research Genetic enhancement Papillomavirus E7 Proteins Cell Apoptosis Biology Viral vector Adenoviridae 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Humans RNA Antisense neoplasms Molecular Biology Cisplatin Human papillomavirus 16 Papillomavirus Infections RNA Transfection Oncogene Proteins Viral female genital diseases and pregnancy complications Antisense RNA Repressor Proteins 030104 developmental biology medicine.anatomical_structure Cell culture Head and Neck Neoplasms 030220 oncology & carcinogenesis Cancer research Molecular Medicine medicine.drug |
Zdroj: | Cancer gene therapy. 25(9-10) |
ISSN: | 1476-5500 |
Popis: | Human papillomavirus (HPV) infection has been identified as an etiologic factor of head and neck cancers (HNCs). We explored the potential use of antisense HPV RNA transcripts for gene therapy and its effect in combination with cisplatin (CDDP) for HPV-positive HNCs. We introduced the antisense RNA transcripts of the E6 and E7 genes of HPV type 16 into UM-SCC-47 cells harboring HPV 16 and YCU-T892 cells that were HPV-negative using a recombinant adenoviral vector, Ad-E6/E7-AS. We then analyzed the effects of the introduction of Ad-E7-AS on cell and tumor growth and the synergistic effect with CDDP in vitro and in vivo. After infection of Ad-E6/E7-AS, the cellular growth of UM-SCC-47 cells were suppressed, but not that of YCU-T892 cells. E7 protein expression was suppressed, and p53 and pRb protein expression increased after infection of Ad-E7-AS. Cell growth and tumorigenicity were greatly suppressed in combination with CDDP compared with Ad-E7-AS or CDDP treatment alone in vitro. Ad-E7-AS combined with CDDP treatment significantly reduced the volumes of established subcutaneous tumors. Transfection with HPV 16 E7 antisense RNA combined with CDDP treatment might be a potentially useful approach to the therapy of HPV 16-positive HNC. |
Databáze: | OpenAIRE |
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