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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Probing the Molecular Mechanisms Governing the Oncolytic Activity of Paeonia suffruticosa on Triple-negative Breast Cancer Cells In Vitro
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Probing the Molecular Mechanisms Governing the Oncolytic Activity of Paeonia suffruticosa on Triple-negative Breast Cancer Cells In Vitro

机译:探讨芍药瘤患者在体外三阴性乳腺癌细胞上的分子机制

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Background/Aim: Extracts of Paeonia suffruticosa are traditionally used in Chinese medicine to increase blood flow. Recently, this extract has been shown to possess anti-tumor and anti-inflammatory properties, though this mechanism remains unknown. In the current work, we prepared extracts of P. suffruticosa and analyzed their effects on MDA-MB-231 triple-negative breast cancer cells. Materials and Methods: Varying concentrations of an aqueous extract of P. suffruticosa was administered to MDA-MB- 231. An MTS assay was used to determine the cell viability. Cytokine production was investigated through enzyme-linked immunosorbent assay (ELISA). Caspase-Glo assays were performed to measure caspase 3/7, 8 and 9 to analyze anti-apoptotic effects. Results: MTS assay for cell viability revealed that the extract increased viability at low concentrations (0.6 mg/ml) and decreased viability observed at concentrations >= 2.5 mg/ml (p<0.01). ELISA for IL-6, IL-2, and TNF-alpha revealed a biphasic dose-response inversely related to viability (p<0.05). IL-24 expression also increased at 2.5 mg/ml and 4.0 mg/ml (p<0.05). Bax levels remained relatively constant while Bcl-2 decreased significantly in all concentrations (p<0.01). Small decreases in Fas ligand levels was observed in parallel with a lack of increase in caspase-8 activity. Most notable was that while 4mg/ml of P. suffruticosa extract reduced MDA-MB-231 viability by >60% (p<0.01), the same concentration reduced the viability of non-transformed HaCat cells by similar to 8% (p>0.05), suggesting a selective oncolytic effect. Conclusion: P. suffruticosa extract has the ability to modulate the production of several tumor suppressive cytokines, induce intrinsic apoptosis and has the capability of reducing cancer burden while sparing healthy tissue.
机译:背景/目的:芍药的提取物传统上用于中药以增加血液流动。最近,已显示该提取物具有抗肿瘤和抗炎特性,尽管该机制仍然未知。在目前的工作中,我们制备了p. suffeticosa的提取物,并分析了它们对MDA-MB-231三阴性乳腺癌细胞的影响。材料和方法:将P. suffuticosa的水提取物的变化浓度不同施用至MDA-MB-231. MTS测定用于确定细胞活力。通过酶联免疫吸附试验(ELISA)研究了细胞因子的产生。进行Caspase-Glo测定以测量Caspase 3 / 7,8和9以分析抗凋亡效应。结果:用于细胞活力的MTS测定表明,提取物在低浓度(0.6mg / ml)下增加可活力,并在浓度下观察到的活力> = 2.5mg / ml(P <0.01)。 IL-6,IL-2和TNF-α的ELISA显示出与活力相反的双相剂量 - 反应(P <0.05)。 IL-24表达也增加了2.5mg / ml和4.0mg / ml(P <0.05)。 BAX水平仍然相对恒定,而BCL-2在所有浓度下显着降低(P <0.01)。在缺乏Caspase-8活性的缺乏增加,观察到Fas配体水平的小降低。最值得注意的是,虽然4mg / ml p. suffeticosa提取物降低MDA-MB-231的活力> 60%(P <0.01),但相同的浓度降低了非转化的HACAT细胞的活力与8%(P> 0.05),表明选择性溶瘤效应。结论:P. suffruticosa提取物能够调节几种肿瘤抑制细胞因子的产生,诱导内在细胞凋亡,并具有降低癌症负担的能力,同时保留健康组织。

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