Intra-tumor injection of lentiviral-vector delivered shRNA targeting human papillomavirus E6 and E7 oncogenes reduces tumor growth in a xenograft cervical cancer model in mice

Abstract

Objectives: HPV is known to play a key role in the growth and maintenance of cervical cancer. Its early genes E6 and E7 can activate several intracellular signal pathways for carcinogenesis. Studies have shown that in vitro knockdown of E6 and E7 can reduce the survival ability of cervical cancer cell lines. In this study, we tested the effect of a lentiviral shRNA against E6/E7 on the tumor growth of xenografted cervical cancer HeLa cells. Methods: In vitro, the growth of HeLa cells transduced with lentiviral shRNA against E6/E7 was compared to controls. In vivo, the RAG-/- mice, which are deficient in T and B lymphocytes were used to establish the HeLa xenografted model. In the treatment group, shRNA against E6/E7 was injected into the tumor directly 30 days after HeLa cell injection when tumors have formed and the injection was repeated at day 60. A lentiviral vector without shRNA was injected in the control group. Results: HeLa cells transduced with lentiviral shRNA against E6/E7 grew slower than those with transduced with the control vector. The difference in growth rate was significant at day 4. We also observed that lentiviral shRNA significantly reduced the size of xenografted tumors compared with controls. The average tumor weight is 60% of the controls.Conclusions: Our results provide evidence that RNAi may be used for the treatment of cervical cancer by intra-tumor injection.