Synergy of a herpes oncolytic virus and paclitaxel for anaplastic thyroid cancer Journal Article
| Authors: | Lin, S. F.; Gao, S. P.; Price, D. L.; Li, S.; Chou, T. C.; Singh, P.; Huang, Y. Y.; Fong, Y.; Wong, R. J. |
| Article Title: | Synergy of a herpes oncolytic virus and paclitaxel for anaplastic thyroid cancer |
| Abstract: | Purpose: Novel therapeutic regimens are needed to improve the dismal outcomes of patients with anaplastic thyroid cancer (ATC). Oncolytic herpes simplex virus have shown promising activity against human ATC. We studied the application of oncolytic herpes simplex virus (G207 and NV1023) in combination with currently used chemotherapeutic drugs (paclitaxel and doxorubicin) for the treatment of ATC. Experimental Design and Results: All four agents showed dose-response cytotoxicity in vitro for the human ATC cell lines KAT4 and DRO90-1. G207, combined with paclitaxel, showed synergistic cytotoxicity. Chou-Talalay combination indices ranged from 0.56 to 0.66 for KAT4, and 0.68 to 0.74 for DRO90-1 at higher affected fractions. Paclitaxel did not enhance G207 viral entry and early gene expression or G207 viral replication. Paclitaxel combined with G207 compared with single-agent treatment or controls showed significantly increased microtubule acetylation, mitotic arrest, aberrant chromatid separation, inhibition of metaphase to anaphase progression, and apoptosis. A single i.t. injection of G207 combined with biweekly i.p. paclitaxel injections in athymic nude mice bearing KAT4 flank tumors showed significantly reduced mean tumor volume (74 ± 38 mm3) compared with G207 alone (388 ± 109 mm3), paclitaxel alone (439 ± 137 mm3), and control (520 ± 160 mm3) groups at 16 days. There was no morbidity in vivo attributable to therapy. Conclusions: Mechanisms of paclitaxel antitumoral activity, including microtubule acetylation, mitotic block, and apoptosis, were enhanced by G207, which also has direct oncolytic effects. Combination of G207 and paclitaxel therapy is synergistic in treating ATC and holds promise for patients with this fatal disease. © 2008 American Association for Cancer Research. |
| Keywords: | controlled study; unclassified drug; human cell; doxorubicin; dose response; drug potentiation; nonhuman; paclitaxel; combined modality therapy; antineoplastic agent; mitosis; mouse; animals; mice; cell survival; apoptosis; gene expression; tumor volume; antineoplastic combined chemotherapy protocols; animal experiment; animal model; cancer cell culture; cytotoxicity; in vitro study; chromatid; blotting, western; fluorescent antibody technique; drug mechanism; nude mouse; mice, nude; nucleotide sequence; carcinoma; herpes virus; simplexvirus; oncolytic viruses; oncolytic virotherapy; anaphase; thyroid cancer; thyroid neoplasms; virus replication; microtubule; metaphase; acetylation; nv 1023; g 207; virus entry; mitosis inhibition |
| Journal Title: | Clinical Cancer Research |
| Volume: | 14 |
| Issue: | 5 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2008-03-01 |
| Start Page: | 1519 |
| End Page: | 1528 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-07-4628 |
| PUBMED: | 18316577 |
| PROVIDER: | scopus |
| PMCID: | PMC2719715 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 10" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Molecular Sequence Numbers: GENBANK: NV1023;" - "Source: Scopus" |
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