Sorafenib combined with ophiopogonin D' inhibits ERK and AKT pathways to promote apoptosis in androgen-independent prostate cancer PC3 cells

Yaowen ZHANG; Zongliang LU; Long LI; Hongxia XU

doi:10.16016/j.1000-5404.202104011

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Sorafenib combined with ophiopogonin D' inhibits ERK and AKT pathways to promote apoptosis in androgen-independent prostate cancer PC3 cells

Basic Medicine | 更新时间：2026-02-13

- Sorafenib combined with ophiopogonin D' inhibits ERK and AKT pathways to promote apoptosis in androgen-independent prostate cancer PC3 cells
- Journal of Third Military Medical University Vol. 43, Issue 19, Pages: 1870-1876(2021)
- 作者机构：
  
  400042 重庆，陆军军医大学(第三军医大学)大坪医院临床营养科
- 作者简介：
- 基金信息：
  
  the General Program of Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0499)
- DOI：10.16016/j.1000-5404.202104011
  CLC： R737.25;R966;R979.1
- Received：02 April 2021，
  
  Revised：2021-06-09，
  
  Published：15 October 2021
- 稿件说明：
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Yaowen ZHANG, Zongliang LU, Long LI, et al. Sorafenib combined with ophiopogonin D' inhibits ERK and AKT pathways to promote apoptosis in androgen-independent prostate cancer PC3 cells[J]. Journal of Third Military Medical University, 2021, 43(19): 1870-1876.
DOI：

Yaowen ZHANG, Zongliang LU, Long LI, et al. Sorafenib combined with ophiopogonin D' inhibits ERK and AKT pathways to promote apoptosis in androgen-independent prostate cancer PC3 cells[J]. Journal of Third Military Medical University, 2021, 43(19): 1870-1876. DOI： 10.16016/j.1000-5404.202104011.

摘要

目的

探讨索拉非尼(sorafenib

Sor)联合麦冬皂苷D'(Ophiopogonin D'，OPD')对雄激素非依赖前列腺癌细胞(PC3细胞)的抗肿瘤效应及其机制。

方法

在体外实验中，Western blot检测不同浓度的OPD' (0、1.0、2.5、5.0 μmol/L)、Sor(0、2.5、5.0、10.0 μmol/L)、OPD' (2.5 μmol/L)+Sor(5.0 μmol/L)联合使用24 h后，对PC3细胞AKT、p-AKT、ERK、p-ERK表达的影响；流式细胞仪Annexin V-FITC和PI双染检测细胞凋亡。在体内实验中，构建PC3细胞异种移植瘤模型后，将裸鼠分为对照组、OPD' 组(1.0 mg/kg)、Sor组(2.5 mg/kg)、OPD' +Sor联合使用组并进行相应干预，且每3天测量裸鼠体质量和肿瘤体积，至药物干预21 d。

结果

Sor主要下调p-AKT蛋白表达及p-AKT/AKT水平(

0.05)，仅在10.0 μmol/L时，降低p-ERK/ERK水平(

0.05)。OPD' 主要下调p-ERK蛋白的表达及p-ERK/ERK水平(

0.05)，仅在5.0 μmol/L时

降低p-AKT/AKT水平(

0.05)。2.5 μmol/L OPD' 和5.0 μmol/L Sor联用时，p-AKT和p-ERK的蛋白表达及p-AKT/AKT和p-ERK/ERK水平均显著降低(

0.05)。细胞凋亡检测结果显示: 两药联用组的凋亡指数明显高于OPD' 或Sor单独用药组(

0.05)。体内实验结果显示: 1.0 mg/kg OPD' 和2.5 mg/kg Sor联用组肿瘤体积和质量均低于其他组(

0.05)。

结论

索拉非尼联合麦冬皂苷D' 通过抑制ERK和AKT通路，促进雄激素非依赖前列腺癌细胞凋亡。

Abstract

Objective

To investigate the anti-tumor effect of sorafenib (Sor) combined with Ophiopogonin D'(OPD') on androgen-independent prostate cancer (PC3) cells and its mechanism.

Methods

In vitro

the exp

ression of AKT

p-AKT

ERK and p-ERK in PC3 cells was detected by Western blotting in 24 h after being treated with different concentrations of OPD' (0

2.5 and 5.0 μmol/L)

Sor (0

2.5

5.0 and 10.0 μmol/L) and OPD' (2.5 μmol/L)+Sor (5.0 μmol/L)

respectively. Apoptosis of PC3 cells was observed by flow cytometry with AnnexinV-FITC and propidium iodide (PI) double staining.

In vivo

PC3 cells xenograft tumor model was constructed in nude mice. Subsequently

24 nude mice were equally divided into control group

OPD' group (1.0 mg/kg)

Sor group (2.5 mg/kg) and OPD' +Sor combined group. The body weight of nude mice and the tumor volume were measured and recorded every 3 days until 21 d after drug intervention.

Results

Sor mainly down-regulated the expression levels of p-AKT and p-AKT/AKT (

0.05)

and only decreased p-ERK/ERK level at the concentration of 10.0 μmol/L (

0.05). While OPD' primarily down-regulated p-ERK and p-ERK/ERK levels (

0.05)

and only reduced p-AKT/AKT at 5.0 μmol/L (

0.05). However

the protein levels of p-AKT

p-ERK

p-AKT/AKT

and p-ERK/ERK were all greatly diminished in the combined group (2.5 μmol/L OPD' +5.0 μmol/L Sor) (

0.05). In addition

the apoptotic index was significantly higher in the combined group than the OPD' or Sor alone group (

0.05). The results of

in vivo

experiments also showed that the tumor volume and tumor weight in the combined group (1.0 mg/kg OPD' +2.5 mg/kg Sor) were much lower than those in the other groups (

0.05).

Conclusion

Sor combined with OPD' promotes apoptosis in PC3 cells by inhibiting ERK and Akt pathways.

关键词

Keywords

references

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