Oncolytic herpes simplex virus and temozolomide synergistically inhibit breast cancer cell tumorigenesis <em>in vitro</em> and <em>in vivo</em>

Fan,Jingjing; Jiang,Hua; Cheng,Lin; Ma,Binlin; Liu,Renbin

doi:10.3892/ol.2020.12360

Oncolytic herpes simplex virus and temozolomide synergistically inhibit breast cancer cell tumorigenesis in vitro and in vivo

Authors:
- Jingjing Fan
- Hua Jiang
- Lin Cheng
- Binlin Ma
- Renbin Liu
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Affiliations: Department of Breast and Neck Surgery, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, Xinjiang 830011, P.R. China, Breast Cancer Center, Department of Breast and Thyroid Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China
Published online on: December 8, 2020 https://doi.org/10.3892/ol.2020.12360
Article Number: 99
Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The oncolytic herpes simplex virus (HSV) G47Δ can selectively eliminate glioblastoma cells via viral replication and temozolomide (TMZ) has been clinically used to treat glioblastoma. However, the combined effect of G47Δ and TMZ on cancer cells, particularly on breast cancer cells, remains largely unknown. The objective of the present study was to investigate the role and underlying mechanism of G47Δ and TMZ, in combination, in breast cancer cell tumorigenesis. The human breast cancer cell lines SK‑BR‑3 and MDA‑MB‑468 were treated with G47Δ and TMZ individually or in combination. Cell viability, flow cytometry, reverse transcription quantitative‑PCR and western blotting were performed to investigate the synergy between G47Δ and TMZ in regulating breast cancer cell behavior in vitro. The role of G47Δ and TMZ in suppressing tumorigenesis in vivo was investigated in a xenograft mouse model. G47Δ and TMZ served a synergistic role resulting in decreased breast cancer cell viability, induction of cell cycle arrest, promotion of tumor cell apoptosis and enhancement of DNA damage response in vitro. The combined administration of G47Δ and TMZ also effectively suppressed breast cancer cell‑derived tumor growth in vivo, compared with the administration of G47Δ or TMZ alone. Synergy between G47Δ and TMZ was at least partially mediated via TMZ‑induced acceleration of G47Δ replication, and such a synergy in breast cancer cells in vitro and in vivo provides novel insight into the future development of a therapeutic strategy against breast cancer.

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