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p38丝裂原活化蛋白激酶信号通路通过G1/G0期阻滞参与提取物诱导的人膀胱癌BFTC-905细胞增殖抑制并在体外引发细胞凋亡。

The p38-MITOGEN-ACTIVATED PROTEIN KINASE Signaling Pathway Is Involved in Extract-Induced Inhibition of the Proliferation of Human Bladder Cancer BFTC-905 Cells via G1/G0 Arrest and Causes Apoptosis In Vitro.

作者信息

Lin Jian-Hui, Hung Chein-Hui, Huang Yun-Ching, Chen Chih-Shou, Ho Dong-Ru

机构信息

Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan.

Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.

出版信息

Pharmaceuticals (Basel). 2023 Sep 22;16(10):1338. doi: 10.3390/ph16101338.

DOI:10.3390/ph16101338
PMID:37895809
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10609973/
Abstract

Bladder cancer is a urothelial malignancy. Bladder cancer starts in the urothelial cells lining the inside of the bladder. The 5-year recurrence rate for bladder cancer ranges from 31% to 78%, and the progression rate is approximately 45%. To treat bladder cancer, intravesical drug therapy is often used. extract (LaE) was obtained from medicinal samples of Chinese motherwort Scientific Chinese Medicine; has various biological effects. This study investigated the impact of LaE on human bladder cancer cells (the BFTC-905 cell line) and the molecular mechanism underlying apoptosis resulting from the activation of cell signal transduction pathways in bladder cancer cells. A cell counting kit-8 (CCK-8) assay was used to determine the effect of LaE on cell growth. The effect of LaE on migration ability was observed using a wound healing assay. The effects of LaE on the cell cycle, reactive oxygen species production, and apoptosis were investigated. Western blot analysis detected apoptosis-related and mitogen-activated protein kinase signaling pathway-related protein concentrations. At non-toxic concentrations, LaE inhibited the proliferation of BFTC-905 cells in a concentration-dependent manner, and the half-maximal inhibitory concentration (IC50) was 24.08172 µg/µL. LaE impaired the migration ability of BFTC-905 cells. LaE arrested the cell cycle in the G1 and G0 phases, increased reactive oxygen species production, and induced apoptosis. LaE increased Bax and p-ERK concentrations and decreased Bcl-2, cleaved caspase-3, and p-p38 concentrations. No differences in PARP, C-PARP, vimentin, e-cadherin, p-JNK, or TNF-alpha concentrations were observed. These results suggest that LaE inhibits the proliferation of human bladder cancer cells. Moreover, the mitogen-activated protein kinase signaling pathway is involved in the inhibition of the proliferation of BFTC-905 cells.

摘要

膀胱癌是一种尿路上皮恶性肿瘤。膀胱癌起源于膀胱内部衬里的尿路上皮细胞。膀胱癌的5年复发率在31%至78%之间,进展率约为45%。为了治疗膀胱癌,常采用膀胱内药物治疗。益母草提取物(LaE)取自益母草中药材样本;具有多种生物学效应。本研究调查了LaE对人膀胱癌细胞(BFTC - 905细胞系)的影响以及膀胱癌细胞中细胞信号转导通路激活导致细胞凋亡的分子机制。使用细胞计数试剂盒 - 8(CCK - 8)测定法来确定LaE对细胞生长的影响。采用伤口愈合测定法观察LaE对迁移能力的影响。研究了LaE对细胞周期、活性氧产生和细胞凋亡的影响。蛋白质免疫印迹分析检测凋亡相关和丝裂原活化蛋白激酶信号通路相关蛋白的浓度。在无毒浓度下,LaE以浓度依赖性方式抑制BFTC - 905细胞的增殖,半数最大抑制浓度(IC50)为24.08172μg/μL。LaE损害了BFTC - 905细胞的迁移能力。LaE使细胞周期停滞在G1和G0期,增加活性氧的产生,并诱导细胞凋亡。LaE增加了Bax和p - ERK的浓度,降低了Bcl - 2、裂解的caspase - 3和p - p38的浓度。未观察到PARP、C - PARP、波形蛋白、E - 钙黏蛋白、p - JNK或TNF - α浓度的差异。这些结果表明LaE抑制人膀胱癌细胞的增殖。此外,丝裂原活化蛋白激酶信号通路参与了对BFTC - 905细胞增殖的抑制。

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