Effect of Paris saponin I on radiosensitivity in a gefitinib-resistant lung adenocarcinoma cell line.

Effect of Paris saponin I on radiosensitivity in a gefitinib-resistant lung adenocarcinoma cell line.
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重楼皂苷 I 对吉非替尼耐药肺腺癌细胞系放射敏感性的影响

DOI:
10.3892/ol.2014.2020
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发表时间:
2014-06
期刊:
影响因子:
2.9
通讯作者:
Ma S
Ma S
中科院分区:
医学4区
文献类型:
--
作者:
Jiang H;Zhao P;Feng J;Su D;Ma S

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先前的研究已经发现,巴黎皂苷I (PSI)具有广泛的药理活性,包括对许多恶性肿瘤(如非小细胞肺癌)的细胞毒活性。本研究旨在探讨PSI治疗对吉非替尼耐药肺腺癌细胞PC-9-ZD的放射增敏作用及其可能的机制。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑测定法测定PSI的生长抑制作用。通过克隆实验确定PSI对PC-9-ZD细胞系的放射增敏作用。使用单命中多目标模型绘制生存曲线并计算致敏增强比。流式细胞术分析细胞周期,荧光素-异硫氰酸-膜联蛋白V/碘化丙啶染色和Hoechst染色分析细胞凋亡。western blotting检测蛋白表达水平。经PSI处理的PC-9-ZD细胞系的增殖明显减少。PSI增强PC-9-ZD细胞的放射敏感性,增敏增强比为1.77。此外,PSI诱导辐照PC-9-ZD细胞G2/M阻滞和凋亡。值得注意的是,在PSI治疗下,b细胞淋巴瘤2 (Bcl-2)下调,caspase-3、Bcl-2样蛋白4 (Bax)和细胞周期蛋白依赖性激酶抑制剂1 (P21waf1/cip1)上调。本研究表明,PSI治疗在体外对吉非替尼耐药PC-9-ZD细胞表现出强大的放射敏感性。这种放射敏感性与细胞周期阻滞在G2/M期有关,并通过caspase-3、Bax和P21waf1/cip1的增加以及Bcl-2产生的减少而导致细胞凋亡。
Previous studies have observed that Paris saponin I (PSI) exerts a wide range of pharmacological activities, including cytotoxic activity against a number of malignancies, such as non-small cell lung cancers. The present study aimed to investigate the radiosensitization of PSI treatment on a gefitinib-resistant lung adenocarcinoma cell line, PC-9-ZD, and its possible mechanism. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to determine the growth inhibition effect of PSI. A clonogenic assay was performed to determine the radiosensitizing effect of PSI treatment on the PC-9-ZD cell line. A single-hit multi-target model was used to plot survival curves and calculate sensitizing enhancement ratios. The cell cycle was analyzed by flow cytometry and cell apoptosis was analyzed with fluorescein-isothiocyanate-Annexin V/propidium iodide and Hoechst staining. The expression levels of the proteins were detected by western blotting. There was a significant reduction observed in the proliferation of the PC-9-ZD cell lines that were treated with PSI. PSI enhanced the radiosensitivity of the PC-9-ZD cells with a sensitization enhancement ratio of 1.77. Furthermore, PSI induced G2/M arrest and apoptosis of the irradiated PC-9-ZD cells. Notably, B-cell lymphoma 2 (Bcl-2) was downregulated, and caspase-3, Bcl-2-like protein 4 (Bax) and cyclin-dependent kinase inhibitor 1 (P21waf1/cip1) were upregulated by the PSI treatment. The present study showed that PSI treatment exhibited potent radiosensitivity against gefitinib-resistant PC-9-ZD cells in vitro. This radiosensitivity was associated with cell cycle arrest at the G2/M phase, and apoptosis via an increase in caspase-3, Bax and P21waf1/cip1 as well as a decrease in Bcl-2 production.
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