title: The oncolytic herpes simplex virus vector, G47Δ, effectively targets tamoxifen-resistant breast cancer cells.
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.
authors.affiliation: Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, P.R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Fan
authors.affiliation: Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, P.R. China.
authors.forename: Renbin
authors.initials: R
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D050130:Oncolytic Virotherapy; D018139:Simplexvirus / Q000235:genetics; D013629:Tamoxifen / Q000008:administration & dosage* / Q000031:analogs & derivatives
chemical_list: D013629:Tamoxifen; C016601:afimoxifene