Highly potent and specific siRNAs against E6 or E7 genes of HPV16- or HPV18-infected cervical cancers.

Abstract:

:Infection with high-risk types (type 16 or type 18) of human papillomaviruses (HPVs) increases a patient's risk of cervical cancer. Given the importance of the cervix and the severe side effects resulting from traditional cancer therapies, this study aimed to achieve targeted inhibition of viral oncogenes in tumor cells using small interfering RNAs (siRNA). To accomplish this, we developed nine siRNAs against either the E6 or E7 genes of HPV-16 or HPV-18 in several combinations, yielding siRNAs targeting 16E6, 16E7, 18E6 and 18E7. We measured the effectiveness of the siRNAs by examining E6 or E7 mRNA expression after transfection of the siRNAs into HPV-positive CaSki (HPV-16) or HeLa (HPV-18) cell lines. We found that the HPV-siRNAs significantly reduced cell growth and colony formation in both cell lines. Flow cytometry analysis revealed a significant increase in apoptosis. The siRNAs had no effect on cell growth, colony formation or apoptosis in HPV-negative C33A cells, demonstrating a lack of off-target effects. In addition, an in vivo xenograft study showed that intra-tumoral injection of the siRNAs reduced tumor growth in BALB/c nude mice. In conclusion, we have developed highly specific and potent HPV-siRNAs that successfully suppress tumor growth and induce apoptosis in HPV-positive cervical cancer cells. siRNA treatment has potential for further development as an adjuvant therapy for cervical cancer.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Chang JT,Kuo TF,Chen YJ,Chiu CC,Lu YC,Li HF,Shen CR,Cheng AJ

doi

10.1038/cgt.2010.38

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

827-36

issue

12

eissn

0929-1903

issn

1476-5500

pii

cgt201038

journal_volume

17

pub_type

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