| Summary: | 碩士 === 長庚大學 === 生化與生醫工程研究所 === 95 === Cervical cancer is the second most common malignancy among women worldwide. Previous infections with high-risk types of human papillomaviruses (HPVs) are a necessary cause of cervical cancer and HPV viral genes E6 and E7 play critical roles for induction of carcinogenesis. E6 protein can target p53 for degradation through the ubiquitin pathway, and E7 protein can inactivate retinoblastoma (pRb).
Giving thought to the importance of cervix and the severe side effects resulting from traditional cancer therapies, this study wants to achieve targeted inhibition of oncogenes in tumor cells based on RNA interference (RNAi).
To this aim, we constructed 4 kinds of siRNAs which are sequence-complementally to each target gene (16E6/16E7; 18E6/18E7). , After transfected these siRNAs into HPV infected cell lines CaSki (HPV-16) and HeLa (HPV-18), we observed downregulation of E6/E7 mRNA and, moreover, obvious decrease in cell growth and increased apoptosis. The vector control or HPV negative cell line C33A were not influenced in comparison. We further proceeded with animal experiments to confirm these siRNAs effects in vivo and found that intra-tumor injection of siRNAs could reduce tumor growth in nude mice. (n=7)
These results suggest that siRNAs indeed have specific inhibition on E6/E7 and accelerate tumor cell death.
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