β-榄香烯调控PI3K/Akt/mTOR信号通路对子宫内膜癌Ishikawa细胞增殖、迁移、侵袭及凋亡的影响

doi:10.11904/j.issn.1002-3070.2023.05.002

实用肿瘤学杂志 ›› 2023, Vol. 37 ›› Issue (5): 395-402.doi: 10.11904/j.issn.1002-3070.2023.05.002

β-榄香烯调控PI3K/Akt/mTOR信号通路对子宫内膜癌Ishikawa细胞增殖、迁移、侵袭及凋亡的影响

庄忆君¹, 孙禹琪², 杨微¹

1.佳木斯大学附属第一医院妇产科(佳木斯 154000);
2.伊春市中心医院妇产科

收稿日期:2023-06-07 修回日期:2023-10-22 出版日期:2023-10-28 发布日期:2024-03-18
通讯作者: 杨微,E-mail:yangweidocter@163.com
作者简介:庄忆君,女,(1991-),硕士研究生,从事妇科肿瘤基础及临床的研究。

Effects of β-elemene regulating the PI3K/Akt/mTOR signaling pathway on the proliferation,migration,invasion and apoptosis of endometrial cancer Ishikawa cells

ZHUANG Yijun¹, SUN Yuqi², YANG Wei¹

1. Department of Obstetrics and Gynecology,The First Affiliated Hospital of Jiamusi University,Jiamusi 154000,China;
2. Department of Obstetrics and Gynecology,Yichun Central Hospital

Received:2023-06-07 Revised:2023-10-22 Online:2023-10-28 Published:2024-03-18

摘要/Abstract

摘要： 目的探讨β-榄香烯对子宫内膜癌Ishikawa细胞生物学行为的影响及其作用机制。方法用不同浓度(0、50、100、150、200、250、300 μg/mL)β-榄香烯处理Ishikawa细胞,应用CCK-8法检测细胞存活率,计算β-榄香烯的半数抑制浓度IC₅₀,确定低、中、高药物处理浓度,并设置0 μg/mL β-榄香烯作为空白对照组,2 μg/mL顺铂阳性对照组。使用AnnexinⅤ-FITC/PI双染法检测细胞凋亡率,通过划痕和Transwell实验检测细胞迁移和侵袭能力,通过Western blot检测Ishikawa细胞中PI3K/Akt/mTOR信号通路相关蛋白的表达水平。结果 β-榄香烯呈浓度依赖性抑制Ishikawa细胞的增殖,其对Ishikawa细胞24 h和48 h的IC₅₀分别为168.9 μg/mL和157.1 μg/mL。β-榄香烯能够诱导Ishikawa细胞的凋亡,在经0、85、170、255 μg/mL β-榄香烯处理24 h后,细胞凋亡率分别为(9.41±0.52)%、(16.67±0.25)%、(21.27±0.30)%和(25.55±0.89)%,组间多重比较具有统计学差异(P＜0.001)。β-榄香烯还能够抑制Ishikawa细胞的迁移、侵袭能力,并且抑制作用随着浓度的升高而增强(P＜0.001)。此外,β-榄香烯可降低Ishikawa细胞PI3K、p-PI3K、mTOR、p-mTOR蛋白表达水平(P＜0.05),p-PI3K和p-mTOR蛋白表达水平显示出明显的浓度依赖性,255 μg/mL β-榄香烯组与0 μg/mL β-榄香烯组相比,PI3K、p-PI3K、Akt、mTOR、p-mTOR蛋白表达水平明显降低(P＜0.001)。结论 β-榄香烯能够抑制子宫内膜癌Ishikawa细胞增殖、迁移和侵袭,促进其凋亡,其机制可能与β-榄香烯能够抑制Ishikawa细胞PI3K/Akt/mTOR信号通路的激活有关。

关键词: β-榄香烯, 子宫内膜癌, Ishikawa细胞, PI3K/Akt/mTOR信号通路

Abstract: Objective The aim of this study was to investigate the effects of β-elemene on the biological behavior of endometrial cancer Ishikawa cells and its mechanism of action. Methods Different concentrations(0,50,100,150,200,250,300 μg/mL)of β-elemene were used to treat Ishikawa cells.The cell viability was measured using the CCK-8 assay to calculate the half-maximal inhibitory concentration(IC₅₀)of β-elemene and to determining low,medium,and high treatment concentrations.A 0 μg/mL of β-elemene was set up a blank control group and 2 μg/mL of cisplatin for a positive control group.The apoptotic rate was detected using Annexin V-FITC/PI double staining.The scratch wound healing assay and Transwell assay were used to detect the abilities of cell migration and invasion.Western blot was performed to evaluate the expression of PI3K/Akt/mTOR signaling pathway related proteins in Ishikawa cells. Results β-Elemene significantly inhibited the proliferation of Ishikawa cells in a dose-dependent manner.The IC₅₀ values of β-elemene at 24 and 48 hours were 168.9 μg/mL and 157.1 μg/mL,respectively.β-Elemene induced apoptosis in Ishikawa cells and after treatment with β-elemene at 0,85,170,and 255 μg/mL for 24 hours,the apoptotic rates of Ishikawa cells were(9.41±0.52)%,(16.67±0.25)%,(21.27±0.30)% and(25.55±0.89)%,respectively.There was a statistically significant difference in multiple comparisons between groups(P＜0.001).β-Elemene inhibited the migration and invasion ability of Ishikawa cells,and the inhibitory effects increased with concentration(P＜0.001).In addition,β-elemene reduced the levels of PI3K,p-PI3K,mTOR and p-mTOR proteins in Ishikawa cells(P＜0.05),and the expression of p-PI3K and p-mTOR proteins showed a significant concentration dependence,and β-elemene at the 255 μg/mL of group showed a significant reduction in the expression of PI3K,p-PI3K,Akt and p-mTOR when compared to the 0 μg/mL of β-elemene group(P＜0.001). Conclusion β-Elemene can inhibit the proliferation,migration,and invasion of endometrial cancer Ishikawa cells,promote their apoptosis,and its mechanism may be related to the inhibitory activation of the PI3K/Akt/mTOR signaling pathway in Ishikawa cells.

Key words: β-Elemene, Endometrial cancer, Ishikawa cells, PI3K/Akt/mTOR signaling pathway

中图分类号:

R737.3

庄忆君, 孙禹琪, 杨微. β-榄香烯调控PI3K/Akt/mTOR信号通路对子宫内膜癌Ishikawa细胞增殖、迁移、侵袭及凋亡的影响[J]. 实用肿瘤学杂志, 2023, 37(5): 395-402.

ZHUANG Yijun, SUN Yuqi, YANG Wei. Effects of β-elemene regulating the PI3K/Akt/mTOR signaling pathway on the proliferation,migration,invasion and apoptosis of endometrial cancer Ishikawa cells[J]. Journal of Practical Oncology, 2023, 37(5): 395-402.

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http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2023/V37/I5/395

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β-榄香烯调控PI3K/Akt/mTOR信号通路对子宫内膜癌Ishikawa细胞增殖、迁移、侵袭及凋亡的影响

Effects of β-elemene regulating the PI3K/Akt/mTOR signaling pathway on the proliferation,migration,invasion and apoptosis of endometrial cancer Ishikawa cells

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