Tetrandrine sensitizes vincristine to induce apoptosis in SGC-7901/VCR cells through MAPK signaling pathway

Ling LEI; Xiuxing JIANG; Yan WANG; Xin DING; Zhiqiang LI; Ning GAO

doi:10.16016/j.2097-0927.202109216

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Tetrandrine sensitizes vincristine to induce apoptosis in SGC-7901/VCR cells through MAPK signaling pathway

Pharmacy | 更新时间：2026-01-09

- Tetrandrine sensitizes vincristine to induce apoptosis in SGC-7901/VCR cells through MAPK signaling pathway
- Journal of Army Medical University Vol. 44, Issue 7, Pages: 691-699(2022)
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)药学与检验医学系生药学与中药学教研室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(31571425)
- DOI：10.16016/j.2097-0927.202109216
  CLC： R735.2;R966;R979.12
- Received：29 September 2021，
  
  Revised：2021-12-11，
  
  Published：15 April 2022
- 稿件说明：
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Ling LEI, Xiuxing JIANG, Yan WANG, et al. Tetrandrine sensitizes vincristine to induce apoptosis in SGC-7901/VCR cells through MAPK signaling pathway[J]. Journal of Army Medical University, 2022, 44(7): 691-699.
DOI：

Ling LEI, Xiuxing JIANG, Yan WANG, et al. Tetrandrine sensitizes vincristine to induce apoptosis in SGC-7901/VCR cells through MAPK signaling pathway[J]. Journal of Army Medical University, 2022, 44(7): 691-699. DOI： 10.16016/j.2097-0927.202109216.

摘要

目的

阐明粉防己碱(tetrandrine)增敏长春新碱(vincristine)诱导胃癌SGC-7901/VCR细胞凋亡的分子机制。

方法

用不同浓度(0、2、4、6、8 μmol/L)粉防己碱及不同浓度(0、50、100、150、200 nmol/L)长春新碱单用或联用处理SGC-7901/VCR细胞48 h，MTT实验检测细胞存活率，流式细胞术检测细胞凋亡。Western blot检测细胞凋亡相关蛋白PARP-1、cleaved-Caspase 9、cleaved-Caspase 3、Bcl-2及MAPK信号通路相关蛋白P38、p-P38、JNK、p-JNK、ERK、p-ERK的表达。应用p38-MAPK抑制剂SB203580、JNK-MAPK抑制剂SP600125或ERK-MAPK抑制剂PD98059预处理SGC-7901/VCR细胞2 h，再以粉防己碱联用长春新碱处理48 h，测定细胞凋亡及相关蛋白表达。粉防己碱及长春新碱单用或联用处理SGC-7901/VCR细胞24 h，流式细胞术检测细胞周期，Western blot检测细胞周期相关蛋白CDC2、p-CDC2的表达。

结果

粉防己碱联用长春新碱导致SGC-7901/VCR细胞增殖活力以剂量依赖的方式下降，联合作用效果为协同。联合用药导致细胞凋亡显著增加(

＜0.05)，与PARP剪切激活及Caspase 9、Caspase 3裂解激活有关。联合用药增强细胞MAPK信号通路p-P38和p-JNK表达，减弱p-ERK表达，应用p38-MAPK或JNK-MAPK通路抑制剂预

处理SGC-7901/VCR细胞后减弱联合用药诱导凋亡的作用(

＜0.05)，而应用ERK-MAPK通路抑制剂预处理后增强联合用药诱导凋亡的作用(

＜0.05)。联合用药导致SGC-7901/VCR细胞S/G

周期阻滞(

＜0.05)。

结论

粉防己碱增敏长春新碱抑制细胞增殖并诱导SGC-7901/VCR细胞凋亡，MAPK信号通路可能在诱导细胞凋亡中起关键作用。

Abstract

Objective

To explore the molecular mechanism of tetrandrine sensitizing vincristine to induce apoptosis of gastric cancer SGC-7901/VCR cells.

Methods

SGC-7901/VCR cells were treated with tetrandrine (0

6 and 8 μmol/L) and vincristine (0

100

150 and 200 nmol/L) alone or in combination for 48 h. MTT assay was used to detect cell viability

and flow cytometry was adopted to observe apoptosis. The expression of apoptosis-related proteins PARP-1

cleaved-Casepase 9

cleaved-Casepase 3

Bcl2

and MAPK signal transduction pathway related proteins P38

p-P38

JNK

p-JNK

ERK and p-ERK were detected by Western blotting. After SGC-7901/VCR cells were pretreated with p38-MAPK inhibitor SB203580

JNK-MAPK inhibitor SP600125

or ERK-MAPK inhibitor PD98059 for 2 h and followed by the treatment of tetrandrine combined with vincristine for 48 h

the apoptosis and the expression levels of related proteins were observed once again. SGC-7901/VCR cells were treated with tetrandrine and vincristine alone or combined for 24 h

cell cycle was detected by flow cytometry

and the expression of CDC2 and p-CDC2 were detected by Western blotting.

Results

Co-administration of tetrandrine and vincristine resulted in decreases in cell viability in a dose-dependent manner in SGC-7901/VCR cells

with a synergistic effect

and led to increases in cell apoptosis (

0.05)

which were associated with degradation of PARP

cleavage/activation of Caspase 3 and Caspase 9. Furthermore

combination of tetrandrine and vincristine markedly increased the levels of phospho-p38 and p

hospho-JNK and decreased the level of phospho-ERK. Pretreatment of p38 inhibitor SB203580 or JNK inhibitor SP600125 attenuated the combination-induced apoptosis (

0.05). In contrast

pretreatment of ERK inhibitor PD98059 potentiated the combination-induced apoptosis (

0.05). Combination treatment caused S/G

cycle block of SGC-7901/VCR cells (

0.05).

Conclusion

Tetrandrine sensitizes vincristine to inhibit cell proliferation and induces apoptosis in SGC-7901/VCR cells. MAPK signaling pathway may play a critical role in the combination-induced apoptosis in the cells.

关键词

Keywords

references

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