胡黄连苷Ⅱ对非小细胞肺癌恶性进展的影响
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篇名: | 胡黄连苷Ⅱ对非小细胞肺癌恶性进展的影响 |
TITLE: | Effect of picroside Ⅱ on the malignant progression of non-small cell lung cancer |
摘要: | 目的 探讨胡黄连苷Ⅱ对非小细胞肺癌(NSCLC)恶性进展的影响及机制。方法将A549细胞分组为对照组,胡黄连苷Ⅱ低、中、高浓度组,K6PC-5[鞘氨醇激酶1(SPHK1)激活剂]组,胡黄连苷Ⅱ高剂量+K6PC-5组,检测细胞增殖、迁移、侵袭情况,以及细胞中增殖细胞核抗原(PCNA)、基质金属蛋白酶2(MMP-2)、MMP-9、SPHK1、1-磷酸鞘氨醇受体3(S1PR3)及胞外信号调节激酶1/2(ERK1/2)蛋白的表达情况。以BALB/c裸鼠为对象,通过皮下接种A549细胞悬液建立NSCLC裸鼠移植瘤模型,并将其分为裸鼠-对照组,裸鼠-胡黄连苷Ⅱ低、中、高剂量组,裸鼠-K6PC-5组,裸鼠-胡黄连苷Ⅱ高剂量+K6PC-5组(每组5只),考察胡黄连苷Ⅱ对其瘤体质量及体积的影响。结果与对照组比较,胡黄连苷Ⅱ低、中、高浓度组的细胞OD450值、EdU阳性细胞率、划痕愈合率、细胞侵袭数及PCNA、MMP-2、MMP-9、SPHK1、S1PR3、ERK1/2蛋白的相对表达量均显著降低;与裸鼠-对照组比较,裸鼠-胡黄连苷Ⅱ低、中、高剂量组裸鼠体内的瘤体质量及体积均显著降低或缩小,上述指标均呈浓度/剂量依赖性变化(P<0.05);K6PC-5组细胞和裸鼠-K6PC-5组裸鼠对应指标的变化趋势则相反(P<0.05)。与胡黄连苷Ⅱ高浓度组或裸鼠-胡黄连苷Ⅱ高剂量组比较,胡黄连苷Ⅱ高浓度+K6PC-5组细胞和裸鼠-胡黄连苷Ⅱ高剂量+K6PC-5组裸鼠的上述定量指标均显著升高或增大(P<0.05)。结论胡黄连苷Ⅱ可能通过抑制SPHK1/1-磷酸鞘氨醇/S1PR3信号通路来抑制NSCLC的恶性进展。 |
ABSTRACT: | OBJECTIVE To investigate the effect and mechanism of picroside Ⅱ on the malignant progression of non-small cell lung cancer (NSCLC). METHODS A549 cells were divided into the control group, picroside Ⅱ low-, medium- and high- concentration groups, K6PC-5 [sphingosine kinase 1 (SPHK1) activator] group, and picroside Ⅱ high-dose+K6PC-5 group. Cell proliferation, migration and invasion were detected. Besides, the expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-2 (MMP-2), MMP-9, SPHK1, sphingosine-1-phosphate receptor 3 (S1PR3) and extracellular signal-regulated kinase 1/2 (ERK1/2) protein in the cells were also observed. BALB/c nude mice were subcutaneously inoculated with A549 cell suspension to establish NSCLC xenograft models. Then they were assigned to the nude mouse-control group, nude mouse-picroside Ⅱ low-, medium- and high-dose groups, nude mouse-K6PC-5 group, and nude mouse-picroside Ⅱ high-dose+K6PC-5 group (with 5 mice in each group) to investigate the effect of picroside Ⅱ on their tumor mass and volume. RESULTS Compared with the control group, the OD450 values, EdU-positive cell rates, scratch healing rates, cell invasion number, and the relative expression levels of PCNA, MMP-2, MMP-9, SPHK1, S1PR3 and ERK1/2 protein in the low-, medium- and high-concentration groups of picroside Ⅱ were significantly decreased. Compared with the nude mouse-control group, the tumor mass and volume in the nude mouse-low-, medium- and high-dose groups of picroside Ⅱ were significantly decreased or shrunk. The changes of above indicators were concentration/dose-dependent (P<0.05). The changing trend of the corresponding indicators in the K6PC-5 ZYTS181) group and the nude mouse-K6PC-5 group was opposite (P<0.05). Compared with the picroside Ⅱ high-concentration group or the nude mice-picroside Ⅱ high-dose group, the above quantitative indicators in the picroside Ⅱ high- concentration+K6PC-5 group cells and the nude mouse-picroside Ⅱ high-dose+K6PC-5 group nude mice were significantly increased or enlarged (P<0.05). CONCLUSIONS Picroside Ⅱ may inhibit the malignant progression of NSCLC by inhibiting SPHK1/sphingosine-1-phosphate/S1PR3 signaling pathway. |
期刊: | 2024年第35卷第04期 |
作者: | 郭寰宇;王卫芳;徐丽伟;董文博 |
AUTHORS: | GUO Huanyu,WANG Weifang,XU Liwei,DONG Wenbo |
关键字: | 胡黄连苷Ⅱ;非小细胞肺癌;增殖;迁移;侵袭;鞘氨醇激酶1/1-磷酸鞘氨醇/1-磷酸鞘氨醇受体3信号通路 |
KEYWORDS: | picroside Ⅱ; non-small cell lung cancer; proliferation; migration; invasion; sphingosine kinase 1/sphingosine-1- |
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