Effect of picroside Ⅱ on the malignant progression of non-small cell lung cancer

GUO Huanyu; WANG Weifang; XU Liwei; DONG Wenbo

doi:10.6039/j.issn.1001-0408.2024.04.09

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Effect of picroside Ⅱ on the malignant progression of non-small cell lung cancer

更新时间：2024-02-23

- Effect of picroside Ⅱ on the malignant progression of non-small cell lung cancer
- ZHONGGUO YAOFANG Vol. 35, Issue 4, Pages: 430-435(2024)
- 作者机构：
  
  1.长春中医药大学临床医学院实验中心，长春　130117
  2.长春中医药大学临床医学院生物化学教研室，长春　130117
  3.长春中医药大学附属医院肿瘤血液科，长春　130112
  4.吉林大学第一医院二部检验科，长春　130061
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.04.09
  CLC： R965
- Published：29 February 2024，
  
  Received：28 August 2023，
  
  Revised：19 December 2023，
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郭寰宇,王卫芳,徐丽伟等.胡黄连苷Ⅱ对非小细胞肺癌恶性进展的影响 ^Δ[J].中国药房,2024,35(04):430-435.

GUO Huanyu,WANG Weifang,XU Liwei,et al.Effect of picroside Ⅱ on the malignant progression of non-small cell lung cancer[J].ZHONGGUO YAOFANG,2024,35(04):430-435.
郭寰宇,王卫芳,徐丽伟等.胡黄连苷Ⅱ对非小细胞肺癌恶性进展的影响 ^Δ[J].中国药房,2024,35(04):430-435. DOI： 10.6039/j.issn.1001-0408.2024.04.09.

GUO Huanyu,WANG Weifang,XU Liwei,et al.Effect of picroside Ⅱ on the malignant progression of non-small cell lung cancer[J].ZHONGGUO YAOFANG,2024,35(04):430-435. DOI： 10.6039/j.issn.1001-0408.2024.04.09.

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OD

450

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（

＜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（

＜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（

＜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 OD

450

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 （

＜0.05）. The changing trend of the corresponding indicators in the K6PC-5 group and the nude mouse-K6PC-5 group was opposite （

＜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 （

＜0.05）.

CONCLUSIONS

Picroside Ⅱ may inhibit the malignant progression of NSCLC by inhibiting SPHK1/sphingosine-1-phosphate/S1PR3 signaling pathway.

关键词

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

non-small cell lung cancerproliferationmigrationinvasionsphingosine kinase 1/sphingosine-1-phosphate/sphingosine-1-phosphate receptor 3 signaling pathway

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