Mobile website
Archive > Volume 24 Issue 5 > 2017,24(5):472-477. DOI:10.3872/j.issn.1007-385X.2017.05.003 Prev Next
Basic Research
Therapeutic effect of the oncolytic vaccinia viruses with expression of mIL-21 on breast cancer of mouse
- Article
- Figures
- Metrics
- Preview PDF
- Reference
- Related
- Cited by
- Materials
Abstract:
Objective:To evaluate the in vitro and in vivo efficacy of tumor-targeted oncolytic vaccinia virus (VV) vectors, VVΔTKΔN1L-RFP and VVΔTKΔN1L-mIL-21, on murine breast cancer cell lines (JC, TUBO and 4T1).Methods: The cytotoxicity of the viruses (VVΔTKΔN1L-RFP and VVΔTKΔN1L-mIL-21) at different mass concentrations on JC, TUBO and 4T1 cells was compared by MTT assay. The replication ability of the two viruses in the three cell lines was tested by TCID50. ELISA assay was performed to detect mIL-21 expression in the supernatants of the culture medium of three cell lines after virus infection. Orthotopic models of triple negative breast cancer (4T1) and Her-2 amplified breast cancer (TUBO) in the BALB/c mice were established to investigate the antitumor efficacy of the two VVs. Results:The two viruses were all able to replicate in breast cancer JC, TUBO and 4T1 cell lines, and low dose of VV caused significant cytotoxicity against breast cancer cell lines. High level of mIL-21 protein was detected in the cell culture supernatants after VVΔTKΔN1L-mIL-21 infection. In the orthotopic 4T1 breast cancer model, the viruses did not show significant anti-tumor effect (P>0.05); however, in the orthotopic TUBO breast cancer model, tumor growth was significantly inhibited by both viruses (P<0.05，P<0.01), and the survival time（P<0.01) of tumor bearing mouse was prolonged in both VVΔTKΔN1L-RFP and VVΔTKΔN1L-mIL-21 treatment group. Conclusion: Both VVΔTKΔN1L-RFP and VVΔTKΔN1L-mIL-21viruses could specifically replicate and showed cell killing effect on breast cancer cells. The two viruses have different in vivo therapeutic effects on Her-2 gene amplified breast cancer and triple negative breast cancer.
Keywords:
Project Supported:
Project supported by the Nature Sciences Foundation of China（No. 81272525，No. 81201792）
Clc Number:
