Fujii Takuma, Saito Miyuki, Iwasaki Eri, Ochiya Takahiro, Takei Yoshifumi, Hayashi Shigenori, Ono Akiko, Hirao Nobumaru, Nakamura Masaru, Kubushiro Kaneyuki, Tsukazaki Katsumi, Aoki Daisuke
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Int J Oncol. 2006 Sep;29(3):541-8.
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.
人乳头瘤病毒（HPV）18不仅与子宫颈鳞状细胞癌有关，还与子宫颈腺癌和小细胞癌有关，已知后者预后较差。在HPV18阳性细胞系中测试了靶向HPV18 E6和E7的小干扰RNA（siRNA），以研究其作用效果和作用机制。还在裸鼠中测试了siRNA与去端胶原蛋白的组合，以确定其是否可能作为一种新的宫颈癌分子靶向治疗方法。将靶向HPV18 E6和E7的siRNAs体外转染到宫颈癌细胞中，并研究其对细胞生长抑制、E6和E7 mRNA表达、视网膜母细胞瘤蛋白表达以及衰老相关β-半乳糖苷酶染色的影响。序列特异性siRNA抑制细胞生长。在转染细胞中观察到E6和E7 mRNA表达下降以及E7蛋白表达下降，但视网膜母细胞瘤蛋白表达和β-半乳糖苷酶染色增加，提示通过衰老产生细胞生长抑制作用。用针对E6和E7的siRNA处理由SKG-II细胞建立的异种移植瘤，明显抑制了体内肿瘤生长。这些结果表明，去端胶原蛋白介导的siRNA HPV18 E6和E7递送可作为宫颈癌的一种新型治疗方法。
