
浏览全部资源
扫码关注微信
1.贵州医科大学 临床医学院,贵阳 550025
2.上海健康医学院 附属周浦医院,上海 201318
3.上海市分子影像学重点实验室,上海 201318
4.上海健康医学院 药学院,上海 201318
5.贵州工程职业学院,贵州 铜仁 554300
罗娇,在读硕士,从事恶性肿瘤及脑转移相关机制研究,E-mail:l287923@163.com
周莉,博士,教授,从事恶性肿瘤及脑转移相关机制研究,E-mail:lzhou_sh@ hotmail.com
收稿日期:2021-01-28,
网络出版日期:2021-05-13,
纸质出版日期:2021-07-05
移动端阅览
罗娇,解伟,张坤驰等.氧化苦参碱对非小细胞肺癌细胞抗肿瘤作用及机制[J].中国实验方剂学杂志,2021,27(13):43-49.
LUO Jiao,XIE Wei,ZHANG Kun-chi,et al.Anti-tumor Effect of Oxymatrine on Non-small Cell Lung Cancer Cell Lines and Its Mechanism[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(13):43-49.
罗娇,解伟,张坤驰等.氧化苦参碱对非小细胞肺癌细胞抗肿瘤作用及机制[J].中国实验方剂学杂志,2021,27(13):43-49. DOI: 10.13422/j.cnki.syfjx.20211396.
LUO Jiao,XIE Wei,ZHANG Kun-chi,et al.Anti-tumor Effect of Oxymatrine on Non-small Cell Lung Cancer Cell Lines and Its Mechanism[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(13):43-49. DOI: 10.13422/j.cnki.syfjx.20211396.
目的
2
研究氧化苦参碱(OM)对非小细胞肺癌(NSCLC)细胞增殖、迁移及侵袭的影响,并探讨其可能的作用机制。
方法
2
使用细胞增殖与活性检测(CCK-8)实验检测OM在不同浓度(0,1.0,2.0,4.0,8.0,16.0,32.0和64.0 mmol·L
-1
)对NSCLC A549和H1299细胞增殖的影响;通过transwell小室法和划痕愈合实验观察不同浓度的OM(8.0,16.0,32.0 mmol·L
-1
)对A549和H1299细胞侵袭与迁移能力的影响;采用蛋白免疫印迹法(Western blot)检测不同浓度OM(8.0,16.0,32.0 mmol·L
-1
)对Notch信号通路相关蛋白的表达水平的影响。
结果
2
OM可有效抑制NSCLC A549和H1299的细胞活力(
P
<
0.05,
P
<
0.01),且呈浓度依赖性;此外,OM可抑制A549和H1299细胞的迁移与侵袭(
P
<
0.01),也呈一定的浓度依赖性。高浓度(32.0 mmol·L
-1
)OM可以明显抑制Notch信号通路中Notch 1细胞内结构域(NICD),转录复合蛋白[肿瘤坏死因子-
α
转化酶(TACE)和无毛重组结合蛋白抑制子(RBPSUH)]及其下游蛋白Hes家族发状分裂相关增强子1(Hes1)的蛋白表达水平。
结论
2
OM可抑制A549和H1299细胞的增殖、迁移和侵袭能力,且可抑制Notch信号通路相关分子的表达。
Objective
2
To investigate the effects of oxymatrine(OM) on proliferation,migration, and invasion of non-small cell lung cancer(NSCLC) A549 and H1299 cells and to explore the possible mechanism.
Method
2
A549 and H1299 cells were treated by OM of different concentrations(0, 1.0,2.0,4.0,8.0,16.0, 32.0, and 64.0 mmol·L
-1
) and the cell viability was detected by cell counting kit-8 (CCK-8) assay. Transwell invasion and wound healing assays were applied to determine the effect of OM of different concentrations (8.0,16.0, and 32.0 mmol·L
-1
) on the invasion and migration of A549 and H1299 cells. Western blot was adopted to detect the changes in the expression of proteins related to the Notch signaling pathway after the treatment by OM of different concentrations (8.0,16.0, and 32.0 mmol·L
-1
).
Result
2
Compared with the control,OM could inhibit the proliferation (
P
<
0.05,
P
<
0.01) and hinder the cell invasion and migration of A549 and H1299 cells (
P
<
0.01) in a dose-dependent manner. The results of Western blot showed that OM(32.0 mmol·L
-1
) could effectively counteract the expression levels of Notch1 intracellular domain(NICD),transcriptional complex proteins [TNF-alpha converting enzyme(TACE) and recombining binding protein suppressor of hairless(RBPSUH)], and Hes family hairy and enhancer of split 1(Hes1) in A549 and H1299 cells.
Conclusion
2
OM was capable of inhibiting the proliferation,migration, and invasion of A549 and H1299 cells and also hindering the expression of proteins related to Notch signaling pathway.
SIEGEL R L , MILLER K D , FUCHS H E , et al . Cancer statistics, 2021 [J]. CA Cancer J Clin , 2021 , 71 ( 1 ): 7 - 33 .
ZHENG R S , SUN K X , ZHANG S W , et al . Report of cancer epidemiology in China, 2015 [J]. Chin J Oncol , 2019 , 41 ( 1 ): 19 - 28 .
PARKIN D M . Global cancer statistics in the year 2000 [J]. Lancet Oncol , 2001 , 2 ( 9 ): 533 - 43 .
ZOU B , ZHOU X L , LAI S Q , et al . Notch signaling and non-small cell lung cancer [J]. Oncol Lett , 2018 , 15 ( 3 ): 3415 - 3421 .
KUBOTA K , KAWAHARA M , OGAWARA M , et al . Vinorelbine plus gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase Ⅲ study [J]. Lancet Oncol , 2008 , 9 ( 12 ): 1135 - 1142 .
DESANTIS C E , LIN C C , MARIOTTO A B , et al . Cancer treatment and survivorship statistics, 2014 [J]. CA Cancer J Clin , 2014 , 64 ( 4 ): 252 - 271 .
LI L , TANG P , LI S , et al . Notch signaling pathway networks in cancer metastasis: a new target for cancer therapy [J]. Med Oncol , 2017 , 34 ( 10 ): 180 .
SIEBEL C , LENDAHL U . Notch signaling in development, tissue homeostasis, and disease [J]. Physiol Rev , 2017 , 97 ( 4 ): 1235 - 1294 .
MEURETTE O , MEHLEN P . Notch signaling in the tumor microenvironment [J]. Cancer Cell , 2018 , 34 ( 4 ): 536 - 548 .
WANG X J , ZHOU R J , ZHANG N , et al . 20( S )-ginsenoside Rg 3 sensitizes human non-small cell lung cancer cells to icotinib through inhibition of autophagy [J]. Eur J Pharmacol , 2019 , 850 : 141 - 149 .
LIU Y , XU Y , JI W , et al . Anti-tumor activities of matrine and oxymatrine: literature review [J]. Tumour Biol , 2014 , 35 ( 6 ): 5111 - 5119 .
LU M L , XIANG X H , XIA S H . Potential signaling pathways involved in the clinical application of oxymatrine [J]. Phytother Res , 2016 , 30 ( 7 ): 1104 - 1112 .
SONG M Q , ZHU J S , CHEN J L , et al . Synergistic effect of oxymatrine and angiogenesis inhibitor NM-3 on modulating apoptosis in human gastric cancer cells [J]. World J Gastroenterol , 2007 , 13 ( 12 ): 1788 - 1793 .
ZHANG Y , PIAO B , ZHANG Y , et al . Oxymatrine diminishes the side population and inhibits the expression of beta-catenin in MCF-7 breast cancer cells [J]. Med Oncol , 2011 , 28 ( Suppl 1 ): S99 - S107 .
LIU Y , BI T , DAI W , et al . Oxymatrine synergistically enhances the inhibitory effect of 5-fluorouracil on hepatocellular carcinoma in vitro and in vivo [J]. Tumour Biol , 2016 , 37 ( 6 ): 7589 - 7597 .
LI S , ZHANG Y , LIU Q , et al . Oxymatrine inhibits proliferation of human bladder cancer T24 cells by inducing apoptosis and cell cycle arrest [J]. Oncol Lett , 2017 , 13 ( 6 ): 4453 - 4458 .
WANG X , LIU C , WANG J , et al . Oxymatrine inhibits the migration of human colorectal carcinoma RKO cells via inhibition of PAI-1 and the TGF-beta1/Smad signaling pathway [J]. Oncol Rep , 2017 , 37 ( 2 ): 747 - 753 .
WU J , CAI Y , LI M , et al . Oxymatrine promotes S -phase arrest and inhibits cell proliferation of human breast cancer cells in vitro through mitochondria-mediated apoptosis [J]. Biol Pharm Bull , 2017 , 40 ( 8 ): 1232 - 1239 .
LI W , YU X , TAN S , et al . Oxymatrine inhibits non-small cell lung cancer via suppression of EGFR signaling pathway [J]. Cancer Med , 2018 , 7 ( 1 ): 208 - 218 .
YU Q , LUO J , ZHANG J , et al . Oxymatrine inhibits the development of non-small cell lung cancer through miR-367-3p upregulation and target gene SGK3 downregulation [J]. Am J Transl Res , 2020 , 12 ( 9 ): 5538 - 5550 .
XU Y , REN H , JIANG J , et al . KIAA0247 inhibits growth, migration, invasion of non-small-cell lung cancer through regulating the Notch pathway [J]. Cancer Sci , 2018 , 109 ( 4 ): 1055 - 1065 .
ANG M K , MOK T S K . Twenty-five years of respirology: advances in lung cancer [J]. Respirology , 2020 , 25 ( 1 ): 26 - 31 .
ZHANG Z , BIEN J , MORI M , et al . A way forward for cancer prevention therapy: personalized risk assessment [J]. Oncotarget , 2019 , 10 ( 64 ): 6898 - 6912 .
LIN B , LI D , ZHANG L . Oxymatrine mediates Bax and Bcl-2 expression in human breast cancer MCF-7 cells [J]. Pharmazie , 2016 , 71 ( 3 ): 154 - 157 .
ALLEN T D , RODRIGUEZ E M , JONES K D , et al . Activated Notch1 induces lung adenomas in mice and cooperates with Myc in the generation of lung adenocarcinoma [J]. Cancer Res , 2011 , 71 ( 18 ): 6010 - 6018 .
LICCIULLI S , AVILA J L , HANLON L , et al . Notch1 is required for Kras-induced lung adenocarcinoma and controls tumor cell survival via p53 [J]. Cancer Res , 2013 , 73 ( 19 ): 5974 - 5984 .
FLEMING R J . Structural conservation of Notch receptors and ligands [J]. Semin Cell Dev Biol , 1998 , 9 ( 6 ): 599 - 607 .
ANDERSSON E R , LENDAHL U . Therapeutic modulation of Notch signalling are we there yet? [J]. Nat Rev Drug Discov , 2014 , 13 ( 5 ): 357 - 378 .
KAGEYAMA R , OHTSUKA T . The Notch-Hes pathway in mammalian neural development [J]. Cell Res , 1999 , 9 ( 3 ): 179 - 188 .
BRUTSCH R , LIEBLER S S , WUSTEHUBE J , et al . Integrin cytoplasmic domain-associated protein-1 attenuates sprouting angiogenesis [J]. Circ Res , 2010 , 107 ( 5 ): 592 - 601 .
WANG Q , REN H , XU Y , et al . GRWD1 promotes cell proliferation and migration in non-small cell lung cancer by activating the Notch pathway [J]. Exp Cell Res , 2020 , 387 ( 2 ): 111806 .
0
浏览量
20
下载量
2
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621