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丁烯基苯酞对人乳腺癌细胞的抗肿瘤和放射增敏作用。

Anti-Tumor and Radiosensitization Effects of N-Butylidenephthalide on Human Breast Cancer Cells.

机构信息

Department of Radiation Oncology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 42743, Taiwan.

Department of Ophthalmology, Hsinchu Mackay Memorial Hospital, Hsinchu 30071, Taiwan.

出版信息

Molecules. 2018 Jan 25;23(2):240. doi: 10.3390/molecules23020240.

Abstract

-Butylidenephthalide (BP), which is extracted from a traditional Chinese medicine, (), displays antitumor activity against various cancer cell lines. The purpose of this study was to investigate the cytotoxic and radiosensitizing effect of BP and the underlying mechanism of action in human breast cancer cells. BP induces apoptosis in breast cancer cells, which was revealed by the TUNEL assay; the activation of caspase-9 and PARP was detected by western blot. In addition, BP-induced G2/M arrest was examined by flow cytometry and the expression levels of the G2/M regulatory protein were detected by western blot. BP also suppresses the migration and invasion of breast cancer cells, which was tested by wound healing and the matrigel invasion assay; the involvement of EMT-related gene expressions was detected by real-time PCR. Furthermore, BP enhanced the radiosensitivity of breast cancer cells, which was measured by the colony formation assay and comet assay, where the foci of γ-H2AX after radiation significantly increased in BP pretreated cells and was evidenced by immunocytochemistry staining and western blot. The homologous recombination (HR) repair protein Rad51 was down-regulated after BP pretreatment. These results indicate that BP might be a potential chemotherapeutic and radiosensitizing agent for breast cancer therapy.

摘要

丁烯基苯酞(BP)是从一种传统中药中提取的,具有抗肿瘤活性,能抑制多种癌细胞系的生长。本研究旨在探讨 BP 对人乳腺癌细胞的细胞毒性和放射增敏作用及其作用机制。TUNEL 检测结果显示 BP 可诱导乳腺癌细胞凋亡,Western blot 检测到 caspase-9 和 PARP 的激活。此外,流式细胞术检测到 BP 诱导的 G2/M 期阻滞,Western blot 检测到 G2/M 期调控蛋白的表达水平。BP 还可抑制乳腺癌细胞的迁移和侵袭,划痕实验和基质胶侵袭实验检测到这一作用,实时 PCR 检测到 EMT 相关基因表达的下调。此外,集落形成实验和彗星实验表明 BP 增强了乳腺癌细胞的放射敏感性,BP 预处理后细胞内 γ-H2AX 焦点明显增加,免疫细胞化学染色和 Western blot 进一步证实了这一点。同源重组(HR)修复蛋白 Rad51 的表达水平在 BP 预处理后下调。这些结果表明,BP 可能是一种有潜力的化疗和放射增敏剂,用于乳腺癌的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dce/6017952/3761a6d63cbe/molecules-23-00240-g001.jpg

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