桂枝茯苓胶囊通过线粒体凋亡途径对骨髓瘤细胞凋亡的影响

SUN Run-jie; XU Jie; GAO Wei; ZHANG Yan-yu; SUN Xiao-qi; JI Lin; CUI Xing

doi:10.1007/s11655-022-3624-6

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桂枝茯苓胶囊通过线粒体凋亡途径对骨髓瘤细胞凋亡的影响

Original Article | Updated：2023-02-01

- 桂枝茯苓胶囊通过线粒体凋亡途径对骨髓瘤细胞凋亡的影响
- Effect of Guizhi Fuling Capsule on Apoptosis of Myeloma Cells Through Mitochondrial Apoptosis Pathway
- 中国结合医学杂志（英文版） 2023年29卷第2期页码：127-136
- Affiliations：
  
  1.Department of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan (250014), China
  2.Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan(250014), China
  3.Department of Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan(250014), China
  4.Department of Neurology, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan (250001), China
  5.Department of Oncology, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan (250001), China
- Author bio：
  
  Prof. CUI Xing, cdz45@foxmail.com
- Funds：
  
  the National Natural Science Foundation of China(82074348);the Taishan Scholar Project(tsqn201812145);the Key Technology Research and Development Program of Shandong(2019GSF108162);the Natural Science Foundation of Shandong Province(ZR2020MH388)
- DOI：10.1007/s11655-022-3624-6
  中图分类号：
- 纸质出版日期：2023-02，
  
  网络出版日期：2022-11-19，
  
  录用日期：2022-05-18
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桂枝茯苓胶囊通过线粒体凋亡途径对骨髓瘤细胞凋亡的影响[J]. 中国结合医学杂志（英文版）, 2023,29(2):127-136.

SUN Run-jie, XU Jie, GAO Wei, et al. Effect of Guizhi Fuling Capsule on Apoptosis of Myeloma Cells Through Mitochondrial Apoptosis Pathway[J]. Chinese Journal of Integrative Medicine, 2023,29(2):127-136.
桂枝茯苓胶囊通过线粒体凋亡途径对骨髓瘤细胞凋亡的影响[J]. 中国结合医学杂志（英文版）, 2023,29(2):127-136. DOI： 10.1007/s11655-022-3624-6.

SUN Run-jie, XU Jie, GAO Wei, et al. Effect of Guizhi Fuling Capsule on Apoptosis of Myeloma Cells Through Mitochondrial Apoptosis Pathway[J]. Chinese Journal of Integrative Medicine, 2023,29(2):127-136. DOI： 10.1007/s11655-022-3624-6.

摘要

目的:

观察桂枝茯苓胶囊 (Guizhi Fuling Capsule

GZFLC) 对骨髓瘤细胞的作用并探讨其机制.

方法:

将MM1S和RPMI 8226细胞与不同浓度的血清共培养

将细胞实验分为阴性对照组 (10%、20%和40%) 、GZFLC组 (10%、20%和40%) 和对照组. 使用细胞计数试剂盒-8和流式细胞术检测骨髓瘤细胞的活性和凋亡水平. 通过ROS试剂盒和JC-1试剂盒来检测GZFLC对骨髓瘤细胞线粒体的影响. Western blot检测凋亡相关蛋白Bcl-2、Bax、Cleaved caspase-3、Cleaved Caspase-9、Cytc和Apaf-1的表达. 将2×10

个RPMI 8226细胞皮下接种于48只裸鼠体内

将小鼠随机分为高、中、低剂量组和对照组

分别给与840、420、210mg/kg/d或等剂量蒸馏水

连续给药15天

观察GZFLC给药组和对照组小鼠的肿瘤体积变化和存活时间. 免疫组化检测瘤体内Cytc和Apaf-1的表达水平.

结果:

GZFLC含药血清抑制了骨髓细胞活性、提高了骨髓细胞凋亡水平 (

0.05) . 此外

GZFLC含药血清提高了细胞内ROS水平并降低了线粒体膜电位 (

0.01) . Western blot显示GZFLC含药血清组Bcl-2/Bax比值降低

Cleaved caspase-3、Cleaved caspase-9、Cytc和Apaf-1的表达水平升高 (

0.01) . 随着时间的推移

GZFLC组小鼠的骨髓瘤体积减小

GZFLC组的小鼠生存时间高于对照组. GZFLC组小鼠荷瘤组织中Cytc和Apaf-1表达水平升高 (

0.05) .

结论:

GZFLC通过线粒体凋亡途径促进骨髓瘤细胞凋亡

并显著减少骨髓瘤小鼠的肿瘤体积、延长小鼠的生存时间.

Abstract

Objective:

To observe the effects of Guizhi Fuling Capsule (GZFLC) on myeloma cells and explore the mechanisms.

Methods:

MM1S and RPMI 8226 cells were co-cultured with different concentrations of serum and the cell experiments were divided into negative (10%

20% and 40%) groups

GZFLC (10%

20%

and 40%) groups and a control group. Cell counting kit-8 (CCK-8) assays and flow cytometry were used to detect the viability and apoptosis levels of myeloma cells. The effects on mitochondria were examined by reactive oxygen specie (ROS) and tetrechloro-tetraethylbenzimidazol carbocyanine iodide (JC-1) assays. Western blot was used to detect the expression of B cell lymphoma-2 (Bcl-2)

Bcl-2-associated X (Bax)

cleaved caspase-3

-9

cytochrome C (Cytc) and apoptotic protease-activating factor 1 (Apaf-1). RPMI 8226 cells (2 × 10

) were subcutaneously inoculated into 48 nude mice to study the

in vivo

antitumor effects of GZFLC. The mice were randomly divided into four groups using a completely randomized design

the high-

medium-

or low-dose GZFLC (840

420

or 210 mg/kg per day

respectively) or an equal volume of distilled water

administered daily for 15 days. The tumor volume changes in and survival times of the mice in the GZFLC-administered groups and a control group were observed. Cytc and Apaf-1 expression levels were detected by immunohistochemistry.

Results:

GZFLC drug serum decreased the viability and increased the apoptosis of myeloam cells (

0.05). In addition

this drug increased the ROS levels and decreased the mitochondrial membrane potential (

0.01). Western blot showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups

whereas the expression levels of cleaved caspase-3

-9

Cytc and Apaf-1 were increased (all

0.01). Over time

the myeloma tumor volumes of the mice in the GZFLC-administered groups decreased

and survival time of the mice in the GZFLC-administered groups were longer than that of the mice in the control group. Immunohistochemical analysis of tumor tissues from the mice in the GZFLC-administered groups revealed that the Cytc and Apaf-1 expression levels were increased (

0.05).

Conclusion:

GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway and significantly reduced the tumor volumes in mice with myeloma

which prolonged the survival times of the mice.

关键词

桂枝茯苓胶囊线粒体细胞凋亡多发性骨髓瘤

Keywords

Guizhi Fuling Capsulemitochondrialapoptosismultiple myeloma

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