Intratumor injection of small interfering RNA-targeting human papillomavirus 18 E6 and E7 successfully inhibits the growth of cervical cancer

Takuma Fujii, Miyuki Saito, Eri Iwasaki, Takahiro Ochiya, Yoshifumi Takei, Shigenori Hayashi, Akiko Ono, Nobumaru Hirao, Masaru Nakamura, Kaneyuki Kubushiro, Katsumi Tsukazaki, Daisuke Aoki

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Human papillomavirus (HPV) 18 is related not only to squamous cell carcinoma of the cervix, but also to adenocarcinoma and small cell carcinoma of the cervix, in which prognosis is known to be poor. Small interfering RNA (siRNA) that targets HPV18 E6 and E7 was tested in HPV18-positive cell lines to investigate its effect and investigate its mechanism of action. Nude mice were also tested in a combination of siRNA and atelocollagen to determine whether it might be useful as a new molecule-targeting therapy for cervical cancer. siRNAs targeting HPV18 E6 and E7 were transfected into cervical cancer cells in vitro and they were investigated for cell growth inhibition, expression of E6 and E7 mRNA, expression of retinoblastoma protein, and senescence-associated β-galactosidase staining. Sequence-specific siRNA inhibited cell growth. Decreased expression of E6 and E7 mRNA followed with E7 protein was observed in the transfected cells, but the expression of retinoblastoma protein and the β-galactosidase staining increased, suggesting cell growth inhibitory effect through senescence. Treatment of xenografts established from SKG-II cells with siRNA specific for E6 and E7 obviously suppressed tumor growth in vivo. These results indicate that atelocollagen-mediated delivery of siRNA HPV18 E6 and E7 can be used as a novel therapeutic approach for cervical cancer.

Original languageEnglish
Pages (from-to)541-548
Number of pages8
JournalInternational Journal of Oncology
Volume29
Issue number3
Publication statusPublished - 2006 Sep

Fingerprint

Human papillomavirus 18
Uterine Cervical Neoplasms
Small Interfering RNA
Injections
Growth
Galactosidases
Retinoblastoma Protein
Cervix Uteri
Staining and Labeling
Messenger RNA
Small Cell Carcinoma
Heterografts
Nude Mice
Squamous Cell Carcinoma
Adenocarcinoma
Therapeutics
Cell Line
Neoplasms
Proteins

Keywords

  • Animal model
  • Atelocollagen
  • Cervical cancer
  • Human papillomavirus
  • Small interfering RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Intratumor injection of small interfering RNA-targeting human papillomavirus 18 E6 and E7 successfully inhibits the growth of cervical cancer. / Fujii, Takuma; Saito, Miyuki; Iwasaki, Eri; Ochiya, Takahiro; Takei, Yoshifumi; Hayashi, Shigenori; Ono, Akiko; Hirao, Nobumaru; Nakamura, Masaru; Kubushiro, Kaneyuki; Tsukazaki, Katsumi; Aoki, Daisuke.

In: International Journal of Oncology, Vol. 29, No. 3, 09.2006, p. 541-548.

Research output: Contribution to journalArticle

Fujii, Takuma ; Saito, Miyuki ; Iwasaki, Eri ; Ochiya, Takahiro ; Takei, Yoshifumi ; Hayashi, Shigenori ; Ono, Akiko ; Hirao, Nobumaru ; Nakamura, Masaru ; Kubushiro, Kaneyuki ; Tsukazaki, Katsumi ; Aoki, Daisuke. / Intratumor injection of small interfering RNA-targeting human papillomavirus 18 E6 and E7 successfully inhibits the growth of cervical cancer. In: International Journal of Oncology. 2006 ; Vol. 29, No. 3. pp. 541-548.
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