Intratumor injection of small interfering RNA-targeting human papillomavirus 18 E6 and E7 successfully inhibits the growth of cervical cancer.
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 beta-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 beta-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.
Fujii
Takuma
T
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. fujiit@sc.itc.keio.ac.jp
Saito
Miyuki
M
Iwasaki
Eri
E
Ochiya
Takahiro
T
Takei
Yoshifumi
Y
Hayashi
Shigenori
S
Ono
Akiko
A
Hirao
Nobumaru
N
Nakamura
Masaru
M
Kubushiro
Kaneyuki
K
Tsukazaki
Katsumi
K
Aoki
Daisuke
D
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D015552:Injections, Intralesional; D051379:Mice; D008819:Mice, Nude; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D016160:Retinoblastoma Protein / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology; D001616:beta-Galactosidase / Q000378:metabolism
D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein; D001616:beta-Galactosidase