黄芪多糖对人乳腺癌MDA-MB-231裸鼠移植瘤生长及肿瘤相关凋亡蛋白的影响

谢荣丹; 孙少伯; 何建新; 董静凝; 龙凤

doi:10.13422/j.cnki.syfjx.20191622

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黄芪多糖对人乳腺癌MDA-MB-231裸鼠移植瘤生长及肿瘤相关凋亡蛋白的影响

药理 | 更新时间：2021-02-09

- 黄芪多糖对人乳腺癌MDA-MB-231裸鼠移植瘤生长及肿瘤相关凋亡蛋白的影响
- Effect of Astragalus Polysaccharide on Growth and Tumor-related Apoptosis Protein of Human Breast Cancer MDA-MB-231 Transplanted Tumor in Nude Mice
- 中国实验方剂学杂志 2019年25卷第16期页码：37-43
- 作者机构：
  
  甘肃中医药大学　中西医结合研究所，甘肃省高校重大疾病分子医学与中医药防治研究省级重点实验室，兰州　 730000
- 作者简介：
  
  谢荣丹，在读硕士，从事中医药防治肿瘤研究，E-mail：rongdanxie6021@163.com
  龙凤，副教授，从事中医药防治肿瘤研究，E-mail: nicole.8808@163.com
- 基金信息：
  
  国家自然科学基金项目(81503377);甘肃省高等学校基本科研业务费专项(998602140604)
- DOI：10.13422/j.cnki.syfjx.20191622
  中图分类号： R22; R242; R2-031; R285.5
- 收稿日期：2019-01-25，
  
  网络出版日期：2019-05-07，
  
  纸质出版日期：2019-08-20
- 稿件说明：
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谢荣丹, 孙少伯, 何建新, 等. 黄芪多糖对人乳腺癌MDA-MB-231裸鼠移植瘤生长及肿瘤相关凋亡蛋白的影响[J]. 中国实验方剂学杂志, 2019,25(16):37-43.

Rong-dan XIE, Shao-bo SUN, Jian-xin HE, et al. Effect of Astragalus Polysaccharide on Growth and Tumor-related Apoptosis Protein of Human Breast Cancer MDA-MB-231 Transplanted Tumor in Nude Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(16): 37-43.
谢荣丹, 孙少伯, 何建新, 等. 黄芪多糖对人乳腺癌MDA-MB-231裸鼠移植瘤生长及肿瘤相关凋亡蛋白的影响[J]. 中国实验方剂学杂志, 2019,25(16):37-43. DOI： 10.13422/j.cnki.syfjx.20191622.

Rong-dan XIE, Shao-bo SUN, Jian-xin HE, et al. Effect of Astragalus Polysaccharide on Growth and Tumor-related Apoptosis Protein of Human Breast Cancer MDA-MB-231 Transplanted Tumor in Nude Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(16): 37-43. DOI： 10.13422/j.cnki.syfjx.20191622.

摘要

目的：

观察黄芪多糖(Astragalus polysaccharides，APS)对人乳腺癌MDA-MB-231裸鼠移植瘤的生长抑制作用及其对肿瘤细胞凋亡的影响，研究APS抑制三阴性乳腺癌MDA-MB-231生长、诱导其凋亡的作用及其分子机制。

方法：

通过将人乳腺癌细胞MDA-MB-231接种于BALB/c-nu雌性裸鼠右侧腋窝皮下建立人乳腺癌裸鼠移植瘤模型；18只乳腺癌荷瘤裸鼠随机分为3组：模型组(每天予生理盐水)，APS低、高剂量组(200，400 mg·kg

－1

)，每组6只；每天灌胃给药200 μL，连续21 d。实验结束，观察比较APS低、高剂量组与模型组荷瘤鼠肿瘤质量、瘤体体积的变化，计算肿瘤抑制率；苏木精-伊红(HE)染色观察瘤体组织细胞形态学变化；原位末端标记法(TUNEL)检测乳腺癌肿瘤组织的凋亡；蛋白免疫印迹法检测肿瘤组织中B细胞淋巴瘤/白血病-2蛋白(Bcl-2)，Bcl-2相关X蛋白(Bax)、半胱天冬氨酸蛋白酶(Caspase)等凋亡相关蛋白表达。

结果：

与模型组比较，APS低、高剂量组中的乳腺癌肿瘤体积、瘤重减小(

0.05

0.01)，其肿瘤抑制率分别为37.9%，57.57%；HE染色观察APS干预组肿瘤组织均呈现明显形态学改变，组织细胞出现凋亡状态；TUNEL染色显示APS组肿瘤组织细胞凋亡率增加；蛋白免疫印迹法发现，与模型组比较，APS低、高剂量组肿瘤组织中Bcl-2蛋白水平下降(

0.05，

0.01)，Bax，Caspase-9，Caspase-7蛋白表达水平上调(

0.05，

0.01)。

结论：

APS能有效抑制MDA-MB-231乳腺癌裸鼠移植瘤生长，诱导人乳腺癌MDA-MB-231细胞发生凋亡，其作用机制与APS影响乳腺癌细胞中凋亡相关蛋白Bcl-2，Bax，Caspase-9，Caspase-7蛋白表达水平有关。

Abstract

Objective:

To observe the inhibitory effect of astragalus polysaccharides (APS) on growth of human breast cancer MDA-MB-231 xenograft tumor in nude mice and its effect on the apoptosis of tumor cells

in order to study the effect of APS on growth and induction of apoptosis of triple negative breast cancer MDA-MB-231 and its possible molecular mechanism.

Method:

Human breast cancer cell MDA-MB-231 was inoculated into the right axillary subcutaneous of BALB/c-nu female nude mice to establish the transplanted tumor model of breast cancer. Eighteen nude mice were randomly divided into 3 groups: model group (saline per day)

low-dose APS group (200 mg·kg

-1

APS per day)

and high-dose APS group (400 mg·kg

-1

APS per day)

with 6 rats in each group. The drug was administered by gavage (200 μL) daily for 21 days. In the experiment

the length and diameter of breast cancer transplanted tumor were measured every two days

and the tumor volume was recorded and calculated. At the end of the experiment

the changes of tumor mass and tumor volume of the low and high-dose APS groups and the model group were observed and compared

and the tumor inhibition rate was calculated. The cell morphology in tumor tissue was observed by hematoxylin-eosin (HE) staining

and Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) was used to verify the apoptosis of breast cancer tissues. The expressions of apoptosis-related proteins

such as B-cell lymphoma/leukemia-2 protein (Bcl-2)

Bcl-2 associated X protein (Bax)

Caspase in tumor tissues was detected by Western blot.

Result:

The tumor volume of breast cancer decreased in the low and high-dose APS groups

and the tumor inhibition rates were 37.9%and 57.57%

respectively

with statistically significant differences from the model group (

0.05

0.01). HE of tumor tissue cells showed that APS led to obvious morphological changes

with apoptosis in the tissue cells. TUNEL staining showed that the apoptosis rate of tumor cells in APS intervention groups was higher than that in control group. Western blot showed that expression of Bcl-2 protein decreased(

0.05

0.01)

and expressions of Bax

Caspase-9 and Caspase-7 were up-regulated(

0.05

0.01)in tumor tissue of APS intervention groups.

Conclusion:

APS can effectively inhibit the growth of MDA-MB-231 breast cancer xenografts in nude mice and induce apoptosis in human breast cancer MDA-MB-231 cells. The mechanism may be related to the effect of APS on expressions of apoptosis-related proteins Bcl-2

Bax

Caspase-9 and Caspase-7 in breast cancer cells.

关键词

Keywords

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