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冷大气等离子体选择性诱导雄激素非依赖性前列腺癌细胞发生G/G期细胞周期阻滞和凋亡。

Cold atmospheric plasma selectively induces G/G cell cycle arrest and apoptosis in AR-independent prostate cancer cells.

作者信息

Hua Dong, Cai Dongyan, Ning Meng, Yu Lihui, Zhang Zhifa, Han Peiyu, Dai Xiaofeng

机构信息

Wuxi People's Hospital, Wuxi 214043, China.

Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.

出版信息

J Cancer. 2021 Aug 17;12(19):5977-5986. doi: 10.7150/jca.54528. eCollection 2021.

Abstract

Androgen receptor-independent prostate cancers do not respond to androgen blockage therapies and suffer from high recurrence rate. We aim to contribute to the establishment of novel therapeutic approaches against such malignancies. We examined whether and how cold atmospheric plasma delivers selectivity against AR-independent prostate cancers via cell viability, transwell assay, wound healing, cell apoptosis assay, flow cytometry, intracellular hydrogen peroxide determination assay, RONS scavenger assay and western blot using human normal epithelial prostatic cells PNT1A and AR-negative DU145 prostate cancer cells. We show that cold atmospheric plasma could selectively halt cell proliferation and migration in androgen receptor-independent cells as a result of induced cell apoptosis and G0/G1 stage cell cycle arrest, and such outcomes were achieved through modulations on the MAPK and NF-kB pathways in response to physical plasma induced intracellular redox level. Our study reports cold atmospheric plasma induced reduction on the proliferation and migration of androgen receptor-independent prostate cancer cells that offers novel therapeutic insights on the treatment of such cancers, and provides the first evidence on physical plasma induced cell cycle G0/G1 stage arrest that warrants the exploration on the synergistic use of cold atmospheric plasma and drugs such as chemotherapies in eradicating such cancer cells.

摘要

雄激素受体非依赖性前列腺癌对雄激素阻断疗法无反应,且复发率高。我们旨在为建立针对此类恶性肿瘤的新型治疗方法做出贡献。我们使用人正常前列腺上皮细胞PNT1A和雄激素受体阴性的DU145前列腺癌细胞,通过细胞活力、Transwell实验、伤口愈合实验、细胞凋亡实验、流式细胞术、细胞内过氧化氢测定实验、活性氧清除剂实验和蛋白质印迹法,研究了冷大气等离子体是否以及如何对雄激素受体非依赖性前列腺癌具有选择性作用。我们发现,冷大气等离子体可通过诱导细胞凋亡和G0/G1期细胞周期阻滞,选择性地抑制雄激素受体非依赖性细胞的增殖和迁移,并且这些结果是通过调节丝裂原活化蛋白激酶(MAPK)和核因子κB(NF-κB)信号通路来响应物理等离子体诱导的细胞内氧化还原水平而实现的。我们的研究报告了冷大气等离子体可诱导雄激素受体非依赖性前列腺癌细胞的增殖和迁移减少,这为治疗此类癌症提供了新的治疗思路,并首次提供了物理等离子体诱导细胞周期G0/G1期阻滞的证据,这值得探索冷大气等离子体与化疗等药物联合使用以根除此类癌细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8662/8408125/3cc7ce76f671/jcav12p5977g001.jpg

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