Fan Jingjing, Jiang Hua, Cheng Lin, Ma Binlin, Liu Renbin
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.
Oncol Lett. 2021 Feb;21(2):99. doi: 10.3892/ol.2020.12360. Epub 2020 Dec 8.
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 . The role of G47Δ and TMZ in suppressing tumorigenesis 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 . The combined administration of G47Δ and TMZ also effectively suppressed breast cancer cell-derived tumor growth , 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 and provides novel insight into the future development of a therapeutic strategy against breast cancer.
溶瘤单纯疱疹病毒（HSV）G47Δ可通过病毒复制选择性清除胶质母细胞瘤细胞，替莫唑胺（TMZ）已在临床上用于治疗胶质母细胞瘤。然而，G47Δ和TMZ联合对癌细胞，特别是对乳腺癌细胞的作用，在很大程度上仍不清楚。本研究的目的是探讨G47Δ和TMZ联合在乳腺癌细胞肿瘤发生中的作用及潜在机制。将人乳腺癌细胞系SK-BR-3和MDA-MB-468分别用G47Δ和TMZ单独或联合处理。进行细胞活力检测、流式细胞术、逆转录定量PCR和蛋白质印迹分析，以研究G47Δ和TMZ在调节乳腺癌细胞行为方面的协同作用。在异种移植小鼠模型中研究G47Δ和TMZ在抑制肿瘤发生中的作用。G47Δ和TMZ发挥协同作用，导致乳腺癌细胞活力降低、诱导细胞周期阻滞、促进肿瘤细胞凋亡并增强DNA损伤反应。与单独给予G47Δ或TMZ相比，联合给予G47Δ和TMZ也有效抑制了乳腺癌细胞衍生的肿瘤生长。G47Δ和TMZ之间的协同作用至少部分是通过TMZ诱导的G47Δ复制加速介导的，这种在乳腺癌细胞中的协同作用为未来抗乳腺癌治疗策略的发展提供了新的见解。
