胡黄连苷Ⅱ对非小细胞肺癌恶性进展的影响

郭寰宇; 王卫芳; 徐丽伟; 董文博

doi:10.6039/j.issn.1001-0408.2024.04.09

您当前的位置：

首页 >

文章列表页 >

胡黄连苷Ⅱ对非小细胞肺癌恶性进展的影响

药学研究 | 更新时间：2024-02-23

- 胡黄连苷Ⅱ对非小细胞肺癌恶性进展的影响
- Effect of picroside Ⅱ on the malignant progression of non-small cell lung cancer
- 中国药房 2024年35卷第4期页码：430-435
- 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：
  
  实验师，硕士。研究方向：生物化学与分子生物学。E-mail：2545363766@qq.com
  副教授，博士。研究方向：药物物质基础及作用机制。E-mail：736792268@qq.com
- 基金信息：
  
  吉林省科技发展计划项目(YDZJ202201-ZYTS181)
- DOI：10.6039/j.issn.1001-0408.2024.04.09
  中图分类号： R965
- 纸质出版日期：2024-02-29，
  
  收稿日期：2023-08-28，
  
  修回日期：2023-12-19，
扫描看全文
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

references

KIM J W，MARQUEZ C P，KOSTYRKO K，et al. Antitumor activity of an engineered decoy receptor targeting CLCF1-CNTFR signaling in lung adenocarcinoma[J]. Nat Med，2019，25（11）：1783-1795.

UPADHYA A，YADAV K S，MISRA A. Targeted drug therapy in non-small cell lung cancer：clinical significance and possible solutions：part Ⅰ[J]. Expert Opin Drug Deliv，2021，18（1）：73-102.

ZHENG J，XU T T，CHEN F，et al. miRNA-195-5p functions as a tumor suppressor and a predictive of poor prognosis in non-small cell lung cancer by directly targeting CIAPIN1[J]. Pathol Oncol Res，2019，25（3）：1181-1190.

ZHU L，CHEN Z，ZANG H J，et al. Targeting c-Myc to overcome acquired resistance of EGFR mutant NSCLC cells to the third-generation EGFR tyrosine kinase inhibitor，osimertinib[J]. Cancer Res，2021，81（18）：4822-4834.

ZHANG X，GUO Q J，LI C H，et al. Immortal time bias-corrected effectiveness of traditional Chinese medicine in non-small cell lung cancer（C-EVID）：a prospective cohort study[J]. Front Oncol，2022，12：845613.

WANG Y K，HONG Y J，ZHANG C Y，et al. Picroside Ⅱ attenuates hyperhomocysteinemia-induced endothelial injury by reducing inflammation，oxidative stress and cell apoptosis[J]. J Cell Mol Med，2019，23（1）：464-475.

张璐，胡莹. 胡黄连苷Ⅱ通过线粒体途径诱导肾癌细胞凋亡的实验研究[J]. 临床肾脏病杂志，2020，20（6）：504-507.

ZHANG L，HU Y. An experimental study renal cancer cell apoptosis induced by picroside Ⅱ through mitochondrial pathway[J]. J Clin Nephrol，2020，20（6）：504-507.

LOU C H，ZHU Z H，XU X T，et al. Picroside Ⅱ，an iridoid glycoside from Picrorhiza kurroa，suppresses tumor migration，invasion，and angiogenesis in vitro and in vivo[J]. Biomed Pharmacother，2019，120：109494.

WANG Y C，TSAI C F，CHUANG H L，et al. Benzyl butyl phthalate promotes breast cancer stem cell expansion via SPHK1/S1P/S1PR3 signaling[J]. Oncotarget，2016，7（20）：29563-29576.

LI F，ZHANG Y F，LIN Z J，et al. Targeting SPHK1/S1PR3-regulated S-1-P metabolic disorder triggers autophagic cell death in pulmonary lymphangiomyomatosis（LAM）[J]. Cell Death Dis，2022，13（12）：1065.

LIU H，ZHANG Z Q，XU M，et al. K6PC-5 activates SphK1-Nrf2 signaling to protect neuronal cells from oxygen glucose deprivation/re-oxygenation[J]. Cell Physiol Biochem，2018，51（4）：1908-1920.

NIU H K，WANG D X，WEN T T，et al. Anwuligan inhi-bits the progression of non-small cell lung cancer via let-7c-3p/PI3K/AKT/mTOR axis[J]. Cancer Med，2023，12（5）：5908-5925.

HEYDARI A H，FATHI M，HEYDARI S，et al. Advanced glycation end product blocker drugs have a great potential to prevent diabetic cardiomyopathy in an animal model of diabetes mellitus type-2[J]. Cardiovasc Ther，2022，2022：7014680.

杨谦，张军，马玉泉，等. 胡黄连苷Ⅱ通过MEK/ERK通路抑制食管癌细胞增殖及侵袭转移的机制研究[J]. 中国医院用药评价与分析，2021，21（7）：820-825.

YANG Q，ZHANG J，MA Y Q，et al. Mechanism of picroside Ⅱ inhibiting proliferation，invasion and metastasis of esophageal cancer cells through MEK/ERK pathway[J]. Eval Anal Drug Use Hosp China，2021，21（7）：820-825.

李佳怿. 探究胡黄连苷Ⅱ对人结直肠癌细胞的抑制作用及其可能的作用机制[D]. 昆明：昆明医科大学，2021.

LI J Y. The inhibitory effect of picroside Ⅱ on colorectal cancer cells and its possible mechanism[D].Kunming：Kunming Medical University，2021.

WANG Y L，WU W R，LIN P L，et al. The functions of PCNA in tumor stemness and invasion[J]. Int J Mol Sci，2022，23（10）：5679.

IBÁÑEZ GASPAR V，MCMORROW T. The curcuminoid EF24 in combination with TRAIL reduces human renal cancer cell migration by decreasing MMP-2/MMP-9 acti-vity through a reduction in H2O2[J]. Int J Mol Sci，2023，24（2）：1043.

文培培，高宇，王晓云，等. 温针疗法联合豨莶草对风湿性关节炎大鼠滑膜细胞活性及SphK1/S1P/S1PR1信号的影响[J]. 针灸临床杂志，2022，38（11）：75-81.

WEN P P，GAO Y，WANG X Y，et al. Effects of warm needling combined with Siegesbeckiae Herba on activity of synovial cells and SphK1/S1P/S1PR1 signaling pathway in rats with RA[J]. J Clin Acupunct Moxibustion，2022，38（11）：75-81.

DAI L，LIU Y X，XIE L，et al. Sphingosine kinase 1/sphingosine-1-phosphate（S1P）/S1P receptor axis is involved in ovarian cancer angiogenesis[J]. Oncotarget，2017，8（43）：74947-74961.

王燕，肖雄，郭峰，等. 和血柔肝方对肝纤维化大鼠SphK1/S1P/S1PR信号通路的影响[J]. 中国中医药信息杂志，2022，29（3）：85-91.

WANG Y，XIAO X，GUO F，et al. Effects of Hexue rougan prescription on SphK1/S1P/S1PR signaling pathway in liver fibrosis rats[J]. Chin J Inf Tradit Chin Med，2022，29（3）：85-91.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

虎杖苷对AML细胞增殖、迁移、侵袭及肿瘤生长的影响

β-谷甾醇对类风湿性关节炎滑膜成纤维细胞功能的影响及机制

连翘醇提物对肺癌NCI-H226细胞增殖、迁移及侵袭的影响

小檗碱通过下调METTL3表达抑制肾癌细胞侵袭和迁移的机制

黄芩苷对脂多糖诱导的人牙周膜干细胞增殖、迁移作用及机制