Abstract
The aim of the present study was to establish a tamoxifen-resistant cell line (MCF-7/TAM-R) and to investigate the therapeutic effect of G47Δ on this cell line both in vitro and in vivo. In the present study, the MCF-7/TAM-R monoclonal subline was established after exposing MCF-7 cells to tamoxifen for 21 days. Then, it was compared with a wild-type MCF-7 subline (MCF-7W), which was not treated with tamoxifen. Cell proliferation, viability, cell cycle and apoptosis analyses were carried out to examine the characteristics of the MCF-7/TAM-R cells. Both in vitro and in vivo toxicity studies were conducted to investigate the therapeutic effect of G47Δ on the MCF-7/TAM-R cells. Compared to the MCF-7W cells, we found that the MCF-7/TAM-R cells exhibited a higher proliferation ability (P<0.05) and a stronger resistance to the cytotoxic effects induced by 4-hydroxytamoxifen (4-OHT) (P<0.05). G47Δ demonstrated a high cytotoxic effect on both the MCF-7/TAM-R and MCF-7W cell lines. After being infected with G47Δ at an MOI of 0.01, >90% of the MCF-7/TAM-R and MCF-7W cells died on day 5. G47Δ induced cell cycle arrest in the G2/M phase. Furthermore, G47Δ inhibited tumor growth in subcutaneous tumor models of both MCF-7/TAM-R and MCF-7W. Thus, we conclude that G47Δ, a third generation oncolytic herpes simplex virus, is highly sensitive and safe in targeting tamoxifen-resistant breast cancer cells both in vitro and in vivo.
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