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Cancer Sci. 2017 Sep;108(9):1870-1880. doi: 10.1111/cas.13316. Epub 2017 Aug 3.

Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction.

Author information

1
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
2
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
3
Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
4
Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
5
Oncolys BioPharma, Inc., Tokyo, Japan.
6
Minimally Invasive Therapy Center, Okayama University Hospital, Okayama, Japan.

Abstract

Osteosarcoma is an aggressive malignant bone tumor that causes bone destruction. Although tumor-specific replicating oncolytic adenovirus OBP-301 induces an antitumor effect in an osteosarcoma tumor, it cannot prevent bone destruction. Zoledronic acid (ZOL) is a clinically available agent that inhibits bone destruction. In this study, we investigated the potential of combination therapy with OBP-301 and ZOL against osteosarcomas with bone destruction. The antitumor activity of OBP-301 and ZOL in monotherapy or combination therapy was assessed using three human osteosarcoma cell lines (143B, MNNG/HOS, SaOS-2). The cytotoxic effect of OBP-301 and/or ZOL was measured by assay of cell apoptosis. The effect of OBP-301 and ZOL on osteoclast activation was investigated. The potential of combination therapy against tumor growth and bone destruction was analyzed using an orthotopic 143B osteosarcoma xenograft tumor model. OBP-301 and ZOL decreased the viability of human osteosarcoma cells. Combination therapy with OBP-301 and ZOL displayed a synergistic antitumor effect, in which OBP-301 promoted apoptosis through suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1). Combination therapy significantly inhibited tumor-mediated osteoclast activation, tumor growth and bone destruction compared to monotherapy. These results suggest that combination therapy of OBP-301 and ZOL suppresses osteosarcoma progression via suppression of MCL1 and osteoclast activation.

KEYWORDS:

Adenovirus; bone destruction; osteosarcoma; telomerase; zoledronic acid

PMID:
28685948
PMCID:
PMC5581539
DOI:
10.1111/cas.13316
[Indexed for MEDLINE]
Free PMC Article

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