title: An oncolytic herpes simplex virus vector, G47Δ, synergizes with paclitaxel in the treatment of breast cancer.
abstract: Paclitaxel-containing treatment regimens are standard chemotherapy schemes for breast cancer patients. The use of oncolytic herpes simplex virus (oHSV) vectors has been shown to be a safe and effective therapeutic approach for different types of cancer. We hypothesized that paclitaxel in combination with an oHSV vector would present an enhanced killing effect when used against breast cancer cells. In the present study, we demonstrated that the combined use of the oHSV vector G47Δ and paclitaxel produced a synergistic effect against breast cancer cells both in vitro and in vivo. In vitro studies demonstrated that paclitaxel and G47Δ both caused dose-dependent cytotoxicity against the human breast cancer cell lines MCF-7 and MDA-MB-468. G47Δ and paclitaxel also demonstrated synergistic cytotoxicity when applied together, with Chou-Talalay combination indices ranging from 0.44 to 0.77 for MCF-7 cells and 0.68 to 0.83 for MDA-MB‑468 cells. Paclitaxel did not enhance viral replication or viral spread among tumor cells. However, G47Δ increased the antitumor ability of paclitaxel by inducing mitotic arrest and apoptosis. In vivo studies indicated that when combined with G47Δ, the dose of paclitaxel could be reduced at least 5-fold while maintaining levels of tumor reduction similar to those achieved with the administration of paclitaxel alone. Combination therapy resulted in no morbidity in vivo. Our data demonstrated that G47Δ and paclitaxel combination therapy had synergistic effects in the treatment of breast cancer. This combination therapy may be promising for breast cancer patients.
authors.affiliation: Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, PR China.
authors.forename: Wei-Gen
authors.initials: WG
authors.lastname: Zeng
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Li
authors.forename: Pan
authors.initials: P
authors.lastname: Hu
authors.forename: Lan
authors.initials: L
authors.lastname: Lei
authors.forename: Jia-Ni
authors.initials: JN
authors.lastname: Wang
authors.forename: Ren-Bin
authors.initials: RB
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002470:Cell Survival; D002522:Chlorocebus aethiops; D003131:Combined Modality Therapy; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D018139:Simplexvirus / Q000235:genetics*; D047368:Tumor Burden / Q000187:drug effects; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel