Effect of Shugan Jianpi Jiedu Prescription Medicated Serum on Proliferation， Migration and Invasion of Triple-negative Breast Cancer MDA-MB-231 Cells Based on PI3K/Akt/mTOR Signaling Pathway

Lin-pei LI; Zhen ZHANG; Bo PAN; Pu-hua ZENG; Zheng-ping BAI

doi:10.13422/j.cnki.syfjx.20211592

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Effect of Shugan Jianpi Jiedu Prescription Medicated Serum on Proliferation， Migration and Invasion of Triple-negative Breast Cancer MDA-MB-231 Cells Based on PI3K/Akt/mTOR Signaling Pathway

Pharmacology | 更新时间：2021-07-15

- Effect of Shugan Jianpi Jiedu Prescription Medicated Serum on Proliferation， Migration and Invasion of Triple-negative Breast Cancer MDA-MB-231 Cells Based on PI3K/Akt/mTOR Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 15, Pages: 22-28(2021)
- 作者机构：
  
  1.湖南中医药大学，长沙 410208
  2.湖南省中医药研究院附属医院，长沙 410006
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20211592
  CLC： R22;R242;R2-031;R730.5
- Received：23 March 2021，
  
  Published Online：11 June 2021，
  
  Published：05 August 2021
- 稿件说明：
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李琳霈,张真,潘博等.基于PI3K/Akt/mTOR信号通路探讨疏肝健脾解毒方含药血清对三阴乳腺癌MDA-MB-231细胞增殖、迁移和侵袭的影响[J].中国实验方剂学杂志,2021,27(15):22-28.

LI Lin-pei,ZHANG Zhen,PAN Bo,et al.Effect of Shugan Jianpi Jiedu Prescription Medicated Serum on Proliferation， Migration and Invasion of Triple-negative Breast Cancer MDA-MB-231 Cells Based on PI3K/Akt/mTOR Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(15):22-28.
李琳霈,张真,潘博等.基于PI3K/Akt/mTOR信号通路探讨疏肝健脾解毒方含药血清对三阴乳腺癌MDA-MB-231细胞增殖、迁移和侵袭的影响[J].中国实验方剂学杂志,2021,27(15):22-28. DOI： 10.13422/j.cnki.syfjx.20211592.

LI Lin-pei,ZHANG Zhen,PAN Bo,et al.Effect of Shugan Jianpi Jiedu Prescription Medicated Serum on Proliferation， Migration and Invasion of Triple-negative Breast Cancer MDA-MB-231 Cells Based on PI3K/Akt/mTOR Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(15):22-28. DOI： 10.13422/j.cnki.syfjx.20211592.

摘要

目的

通过体外细胞实验研究疏肝健脾解毒方对三阴乳腺癌治疗的有效性和可能机制。

方法

实验设置正常血清组、吡柔比星组和低、中、高剂量疏肝健脾解毒方含药血清组。将20只SD大鼠随机分成4组，按照体表面积换算分别予以16.8，8.2，4.05 g·kg

-1

的疏肝健脾解毒方药液和等体积的生理盐水灌胃制备血清。取血清配置各组药液后，分别处理MDA-MB-231细胞。利用细胞增殖与活性检测-8（CCK-8），细胞划痕法和细胞侵袭实验（transwell）法检测其增殖、迁移和侵袭能力，通过蛋白免疫印迹法（Western blot）检测MDA-MB-231细胞中磷脂酰肌醇3-激酶（PI3K），蛋白激酶B（Akt）和雷帕霉素靶蛋白（mTOR）蛋白表达水平。

结果

与正常血清组比较，3种不同剂量的含药血清组和吡柔比星组均能抑制细胞的增殖（

0.01），且中、高剂量含药血清组与吡柔比星组间差异无统计学意义。与正常血清组比较，3种不同剂量的含药血清组和吡柔比星组均能显著减缓划痕的愈合（

0.01），但含药血清组较吡柔比星组弱（

0.05，

0.01）。与正常血清组比较，3种不同剂量的含药血清组和吡柔比星组均能减少侵入transwell小室下室的细胞数（

0.01），且中、高剂量含药血清组与吡柔比星组间差异无统计学意义。Western blot结果显示，与正常血清组比较，经3种不同剂量的含药血清组和吡柔比星组处理48 h后，细胞中的PI3K，Akt和mTOR蛋白表达均降低（

0.01）。

结论

疏肝健脾解毒汤含药血清能抑制三阴乳腺癌MDA-MB-231细胞的迁移和侵袭能力，其机制可能与下调PI3K/Akt/mTOR信号通路中的蛋白表达有关。

Abstract

Objective

To study the efficacy and mechanism of Shugan Jianpi Jiedu prescription （SJJ） in the treatment of triple-negative breast cancer through

in vitro

cell experiments.

Method

The following groups were set up in this study： a normal serum group，a pirarubicin group，and low-，medium-， and high-dose SJJ-medicated serum groups. Twenty SD rats were randomly divided into four groups and administered with SJJ solution （16.8，8.2，4.05 g·kg

-1

） and normal saline （equal volume） according to the body surface area to prepare serum. MDA-MB-231 cells were treated separately. The proliferation， migration and invasion of MDA-MB-231 cells were detected by the cell counting kit-8（CCK-8），wound healing assay and transwell cell invasion assay. The phosphoinositide 3-kinase （PI3K），protein kinase B （Akt）， and mechanistic target of rapamycin （mTOR） protein expression levels in MDA-MB-231 cells were tested by the Western blot.

Result

The cell proliferation in the three different doses of medicated serum groups and the pirarubicin positive control group was significantly inhibited as compared with that in the normal serum group（

0.01），and there was no statistical difference for this between the medium/high dose medicated serum group and the pirarubicin positive control group.The wound healing in the SJJ-medicated serum groups and the pirarubicin group was slowed down as compared with that in the normal serum group （

0.01），and the effect in the SJJ-medicated serum groups was weaker than that in the pirarubicin group （

0.05，

0.01）. The number of cells invading the lower transwell chamber was decreased as compared with that in the normal serum group （

0.01），and there was no statistical difference between the medium-/high-dose SJJ-medicated serum groups and the pirarubicin group. Western blot results showed that 48 h after treatment，the PI3K，Akt， and mTOR expression levels in the cells of SJJ-medicated serum groups and the pirarubicin group were lower than those of the normal serum group（

0.01）.

Conclusion

The SJJ-medicated serum could inhibit the proliferation， migration and invasion of MDA-MB-231 cells presumedly by down-regulating the protein expression levels in the PI3K/Akt/mTOR signaling pathway.

关键词

Keywords

references

FERLAY J ， SOERJOMATARAM I ， DIKSHIT R ， et al . Cancer incidence and mortality worldwide：sources，methods and major patterns in GLOBOCAN 2012 ［J］. Int J Cancer ， 2015 ， 136 （ 5 ）： E359 - E386 .

BRAY F ， FERLAY J ， SOERJOMATARAM I ， et al . Global cancer statistics 2018：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries ［J］. CA Cancer J Clin ， 2018 ， 68 （ 6 ）： 394 - 424 .

DAWSON S J ， PROVENZANO E ， CALDAS C . Triple negative breast cancers：clinical and prognostic implications ［J］. Eur J Cancer ， 2009 ， 45 （ Suppl 1 ）： 27 - 40 .

JIA H ， TRUICA C I ， WANG B ， et al . Immunotherapy for triple-negative breast cancer：existing challenges and exciting prospects ［J］. Drug Resist Updat ， 2017 ， 32 ： 1 - 15 .

WAKS A G ， WINER E P . Breast cancer treatment ［J］. JAMA ， 2019 ， 321 （ 3 ）： 316 .

MONTERO J C ， ESPARIS-OGANDO A ， RE-LOUHAU M F ， et al . Active kinase profiling，genetic and pharmacological data define mTOR as an important common target in triple-negative breast cancer ［J］. Oncogene ， 2014 ， 33 （ 2 ）： 148 - 156 .

KANDULA M ， CH K K ， YS A R . Molecular mechanism and targeted therapy options of triple-negative （ER，PgR，HER-2/neu） breast cancer：review ［J］. World J Oncol ， 2013 ， 4 （ 3 ）： 137 - 141 .

李琳霈，杨晓，潘博，等 . 疏肝健脾解毒方对人乳腺癌细胞MCF-7增殖及凋亡的影响［J］. 湖南中医药大学学报， 2018 ， 38 （ 6 ）： 645 - 649 .

李琳霈，杨晓，王容容，等 . 疏肝健脾解毒方对乳腺癌癌前病变肝郁证大鼠模型乳腺组织血管生成的影响［J］. 湖南中医药大学学报， 2019 ， 39 （ 10 ）： 1195 - 1199 .

李琳霈，杨晓，王容容，等 . 疏肝健脾解毒方对乳腺癌癌前病变肝郁证大鼠模型乳腺组织性激素受体和脏器系数的影响［J］. 时珍国医国药， 2019 ， 30 （ 5 ）： 1073 - 1075 .

王鹏波，代云云，董涵，等 . 中医药干预乳腺癌治疗的研究进展［J］. 中国实验方剂学杂志， 2021 ， 27 （ 7 ）： 235 - 243 .

COSTA R L B ， HAN H S ， GRADISHAR W J ． Targeting the PI3K /AKT / mTOR pathway in triple-negative breast cancer：a review ［J］． Breast Cancer Res Treat ， 2018 ， 169 （ 3 ）： 397 - 406 ．

ENGELMAN J A ， LUO J ， CANTLEY L C . The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism ［J］. Nat Rev Genet ， 2006 ， 7 （ 8 ）： 606 - 619 .

FRUMAN D A ， CHIU H ， HOPKINS B D ， et al . The PI3K pathway in human disease ［J］. Cell ， 2017 ， 170 （ 4 ）： 605 - 635 .

LORUSSO P M . Inhibition of the PI3K/AKT/mTOR pathway in solid tumors ［J］. J Clin Oncol ， 2016 ， 34 （ 31 ）： 3803 - 3815 .

ENGELMAN J A . Targeting PI3K signalling in cancer：opportunities，challenges and limitations ［J］. Nat Rev Cancer ， 2009 ， 9 （ 8 ）： 550 - 562 .

GUERRERO-ZOTANO A ， MAYER I A ， ARTEAGA C L . PI3K/AKT/mTOR：role in breast cancer progression，drug resistance，and treatment ［J］. Cancer Metastasis Rev ， 2016 ， 35 （ 4 ）： 515 - 524 .

ZAYTSEVA Y Y ， VALENTINO J D ， GULHATI P ， et al . mTOR Inhibitors in cancer therapy ［J］. Cancer Lett ， 2012 ， 319 （ 1 ）： 1 - 7 .

SAXTON R A ， SABATINI D M . mTOR signaling in growth，metabolism，and disease ［J］. Cell ， 2017 ， 168 （ 6 ）： 960 - 976 .

CHEN Q Y ， COSTA M . PI3K/Akt/mTOR signaling pathway and the biphasic effect of arsenic in carcinogenesis ［J］. Mol Pharmacol ， 2018 ， 94 （ 1 ）： 784 - 792 .

LEE K ， NAM K T ， CHO S H ， et al . Vital roles of mTOR complex 2 in notch-driven thymocyte differentiation and leukemia ［J］. J Exp Med ， 2012 ， 209 （ 4 ）： 713 - 728 .

GUPTA S ， HAU A M ， BEACH J R ， et al . Mammalian target of rapamycin complex 2 （mTORC2） is a critical determinant of bladder cancer invasion ［J］. PLoS One ， 2013 ， 8 （ 11 ）： e81081 .

DRISCOLL D R ， KARIM S A ， SANO M ， et al . mTORC2 signaling drives the development and progression of pancreatic cancer ［J］. Cancer Res ， 2016 ， 76 （ 23 ）： 6911 - 6923 .

BALKO J M ， GILTNANE J M ， WANG K ， et al . Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets ［J］. Cancer Discov ， 2014 ， 4 （ 2 ）： 232 - 245 .

MORRISON J M ， HICKS D J ， JONES B ， et al . Rictor/mTORC2 drives progression and therapeutic resistance of HER2-amplified breast cancers ［J］. Cancer Res ， 2016 ， 76 （ 16 ）： 4752 - 4764 .

周慧灵，刘铸，黎雪，等 . 中医视角下的恶性肿瘤患者症状群研究进展［J］. 世界中医药， 2020 ， 15 （ 8 ）： 1218 - 1220 .

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