Open Access

Eradication of cervical cancer in vivo by an AAV vector that encodes shRNA targeting human papillomavirus type 16 E6/E7

  • Authors:
    • Naoto Sato
    • Yasushi Saga
    • Ryosuke Uchibori
    • Tomonori Tsukahara
    • Masashi Urabe
    • Akihiro Kume
    • Hiroyuki Fujiwara
    • Mitsuaki Suzuki
    • Keiya Ozawa
    • Hiroaki Mizukami
  • View Affiliations

  • Published online on: January 15, 2018     https://doi.org/10.3892/ijo.2018.4245
  • Pages: 687-696
  • Copyright: © Sato et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The major causative agent of cervical cancer is human papilloma virus (HPV); the viral proteins E6 and E7 induce carcinogenesis through the inactivation of the host tumor-suppressor gene. Therefore, the stable expression of specific inhibitors of E6 and E7 in cancer cells is expected to provide effective treatment for cervical cancer without affecting normal tissue. In this study, we propose a novel therapeutic approach using an adeno-associated virus (AAV) vector encoding short hairpin RNA (shRNA) against the oncoproteins E6 and E7 (shE6E7) of HPV type 16 (HPV‑16), termed AAV‑shE6E7. Three different HPV‑16-positive cervical cancer cell lines (BOKU, SiHa and SKG-IIIa cells) were tested for gene transfer efficiency using serotypes of AAV vectors. For in vitro analysis, the cells were transduced AAV‑shE6E7; alternatively, in vivo studies were performed via the administration of a direct injection of AAV‑shE6E7 into cervical cancer cell-derived tumors in mice. The high gene transfer efficiency was observed using AAV2 in all three cervical cancer cell lines. Following transduction, we observed apoptosis, G1 phase arrest and cell growth inhibition. Additionally, in the transduced cells, the E6, E7 and p16 expression levels decreased, whereas the expression levels of p53, p21 and pRb levels were enhanced. The growth of subcutaneously transplanted tumors was markedly inhibited by the single administration of AAV2‑shE6E7, and the tumors were almost completely eradicated without any adverse effects. These results provided evidence of the utility of AAV2‑shE6E7 as a novel treatment approach for cervical cancer.
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March-2018
Volume 52 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Sato N, Saga Y, Uchibori R, Tsukahara T, Urabe M, Kume A, Fujiwara H, Suzuki M, Ozawa K, Mizukami H, Mizukami H, et al: Eradication of cervical cancer in vivo by an AAV vector that encodes shRNA targeting human papillomavirus type 16 E6/E7. Int J Oncol 52: 687-696, 2018
APA
Sato, N., Saga, Y., Uchibori, R., Tsukahara, T., Urabe, M., Kume, A. ... Mizukami, H. (2018). Eradication of cervical cancer in vivo by an AAV vector that encodes shRNA targeting human papillomavirus type 16 E6/E7. International Journal of Oncology, 52, 687-696. https://doi.org/10.3892/ijo.2018.4245
MLA
Sato, N., Saga, Y., Uchibori, R., Tsukahara, T., Urabe, M., Kume, A., Fujiwara, H., Suzuki, M., Ozawa, K., Mizukami, H."Eradication of cervical cancer in vivo by an AAV vector that encodes shRNA targeting human papillomavirus type 16 E6/E7". International Journal of Oncology 52.3 (2018): 687-696.
Chicago
Sato, N., Saga, Y., Uchibori, R., Tsukahara, T., Urabe, M., Kume, A., Fujiwara, H., Suzuki, M., Ozawa, K., Mizukami, H."Eradication of cervical cancer in vivo by an AAV vector that encodes shRNA targeting human papillomavirus type 16 E6/E7". International Journal of Oncology 52, no. 3 (2018): 687-696. https://doi.org/10.3892/ijo.2018.4245