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低浓度三氟拉嗪促进神经胶质瘤细胞增殖并减少钙依赖性细胞凋亡。

Low concentration trifluoperazine promotes proliferation and reduces calcium-dependent apoptosis in glioma cells.

机构信息

Department of Pathology, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, China.

Department of Pathology, Qingyuan People's Hospital, Jinan University, Qingyuan, 511518, China.

出版信息

Sci Rep. 2018 Jan 18;8(1):1147. doi: 10.1038/s41598-018-19413-y.

DOI:10.1038/s41598-018-19413-y
PMID:29348654
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5773581/
Abstract

Glioma patients constitute the greatest percentage of depressed neoplasm patients. These patients often require antidepressant treatment, but the effect of antidepressant drugs on glioma cells requires further evaluation. In the present study, we evaluated the effect of trifluoperazine (TFP) on the proliferation and apoptosis of glioma cells. Transcriptomic and bioinformatics analysis results suggested that antidepressant drugs, especially TFP, may upregulate the drug-resistant ability of glioma cells. A low concentration of TFP upregulated the viability of glioma cells. Colony formation and EdU assays confirmed that TFP treatment accelerates glioma cell proliferation, but no significant difference was found in the cell cycle distribution of glioma cells after treatment with TFP or control. Flow cytometry and TUNEL staining results suggested that TFP treatment decreased apoptosis in glioma cells. In addition, TFP treatment downregulated the intracellular Ca concentration of glioma cells. In vivo experimental results indicated that TFP treatment promoted proliferation and reduced apoptosis in xenograft tumours in nude mice. Taken together, our results suggest that a low concentration of TFP promotes proliferation and reduces apoptosis in glioma cells both in vitro and in vivo. The potential harmful effects of antidepressant drugs on gliomas require further evaluation before their use in glioma patients.

摘要

神经胶质瘤患者构成了抑郁性肿瘤患者的最大比例。这些患者通常需要抗抑郁治疗,但抗抑郁药物对神经胶质瘤细胞的影响需要进一步评估。在本研究中,我们评估了三氟拉嗪(TFP)对神经胶质瘤细胞增殖和凋亡的影响。转录组学和生物信息学分析结果表明,抗抑郁药,尤其是 TFP,可能上调神经胶质瘤细胞的耐药能力。低浓度的 TFP 上调了神经胶质瘤细胞的活力。集落形成和 EdU 检测证实,TFP 处理加速了神经胶质瘤细胞的增殖,但 TFP 或对照处理后神经胶质瘤细胞的细胞周期分布没有显著差异。流式细胞术和 TUNEL 染色结果表明,TFP 处理减少了神经胶质瘤细胞的凋亡。此外,TFP 处理降低了神经胶质瘤细胞的细胞内 Ca 浓度。体内实验结果表明,TFP 处理促进了裸鼠异种移植瘤的增殖,减少了凋亡。综上所述,我们的结果表明,低浓度的 TFP 促进了体外和体内神经胶质瘤细胞的增殖和减少了凋亡。在将抗抑郁药用于神经胶质瘤患者之前,需要进一步评估它们对神经胶质瘤的潜在有害影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/ac41a8b664e4/41598_2018_19413_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/d0cd7cc8d17d/41598_2018_19413_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/0be44423c038/41598_2018_19413_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/1f73f070976b/41598_2018_19413_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/649f888b712c/41598_2018_19413_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/5562df937b12/41598_2018_19413_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/4f2b6129cd58/41598_2018_19413_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/ac41a8b664e4/41598_2018_19413_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/d0cd7cc8d17d/41598_2018_19413_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/0be44423c038/41598_2018_19413_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/1f73f070976b/41598_2018_19413_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/649f888b712c/41598_2018_19413_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/5562df937b12/41598_2018_19413_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/4f2b6129cd58/41598_2018_19413_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aad/5773581/ac41a8b664e4/41598_2018_19413_Fig7_HTML.jpg

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