Intratumor injection of small interfering RNA-targeting human papillomavirus 18 E6 and E7 successfully inhibits the growth of cervical cancer
2006
Human papillomavirus (HPV) 18 is related not only to squamous cell carcinoma of the cervix, but also to adenocarcinoma and
small cell carcinomaof 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 HPV 18 E6 and E7 were transfected into cervical cancer cells in vitro and they were investigated for
cell growthinhibition, expression of E6 and E7 mRNA, expression of
retinoblastoma protein, and senescence-associated β-
galactosidasestaining. 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 proteinand the β-
galactosidasestaining increased, suggesting
cell growthinhibitory 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 HPV 18 E6 and E7 can be used as a novel therapeutic approach for cervical cancer.
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