岩大戟内酯B通过阻断PI3K/Akt/NF-κB通路抑制结肠癌细胞的增殖和转移

doi:10.12092/j.issn.1009-2501.2021.03.002

中国临床药理学与治疗学 ›› 2021, Vol. 26 ›› Issue (3): 250-257.doi: 10.12092/j.issn.1009-2501.2021.03.002

岩大戟内酯B通过阻断PI3K/Akt/NF-κB通路抑制结肠癌细胞的增殖和转移

陈林俊^1,2，陈文斌¹

¹浙江大学医学院附属第一医院外科，杭州 310003，浙江；²浙江省青春医院外科，杭州 310020，浙江

收稿日期:2020-03-18 修回日期:2020-08-24 出版日期:2021-03-26 发布日期:2021-04-06
通讯作者: 陈文斌，男，博士，主任医师，研究方向：消化道肿瘤。 Tel: 13396553806 E-mail: wenbinchen@zju.edu.cn
作者简介:陈林俊，男，本科，主治医师，研究方向：消化道肿瘤。 Tel: 13588029120 E-mail: chenlinjun9191@163.com
基金资助:
浙江省自然科学基金重点项目（LZ16H160003）

Jolkinolide B inhibits the proliferation and metastasis of colon cancer cells via blocking PI3K/Akt/NF-κB pathway

CHEN Linjun^1,2, CHEN Wenbin¹

¹Department of Surgery, the First Affiliated Hospital of Zhejiang University Medical College, Hangzhou 310003, Zhejiang, China; ² Department of Surgery, Zhejiang Youth Hospital, Hangzhou 310020, Zhejiang, China

Received:2020-03-18 Revised:2020-08-24 Online:2021-03-26 Published:2021-04-06

摘要/Abstract

摘要： 目的：研究岩大戟内酯B（JB）对结肠癌HT-29细胞增殖和转移的抑制作用及其作用机制。方法：用不同浓度JB处理HT-29细胞，采用MTT法检测细胞增殖率；平板克隆实验检测细胞克隆形成率；流式细胞仪检测细胞周期变化；划痕实验分析细胞的迁移能力；Transwell小室实验研究细胞的侵袭能力；免疫荧光法和Western blotting法检测E-钙黏蛋白（E-cadherin）、N-钙黏蛋白（N-cadherin）、波形蛋白vimentin、锌指蛋白（Snail）1、Snail2、基质金属蛋白酶（MMP）-2和MMP-9蛋白的表达；Western blotting法检测p-PI3K、PI3K、p-Akt、Akt、NF-κB P65、p-NF-κB P65蛋白表达水平。100 μg/L IGF-1组和100 μg/L IGF-1+20 μmol/L JB组分别处理HT-29细胞，Western blotting法检测PI3K/Akt/NF-κB通路相关蛋白表达变化。结果：JB抑制HT-29细胞增殖作用浓度依赖性，其作用24 h的IC50为52.68 μmol/L；JB呈浓度依赖性地降低HT-29细胞的克隆形成率（P<0.05）；与对照组相比，JB处理后的HT-29细胞G0/G1期比例显著增高，S期细胞比例明显下降；JB可显著抑制HT-29细胞的体外迁移、侵袭能力（P<0.05）；JB作用后的HT-29细胞E-cadherin蛋白水平升高，vimentin、Snail1、Snail2、N-cadherin、MMP-2、MMP-9、p-PI3K、p-Akt、p-NF-κB P65蛋白表达水平显著降低（P<0.05）；IGF-1+JB组p-PI3K、p-Akt、与p-NF-κB P65蛋白的表达水平较IGF-1组显著下降（P<0.05）。结论：JB在体外能抑制HT-29细胞增殖，诱导细胞在G0/G1期阻滞，抑制HT-29迁移和侵袭，调控上皮-间质转化（EMT）及MMPs，其机制可能与阻断PI3K/Akt/NF-κB通路有关。

关键词: 岩大戟内酯B, HT-29细胞, 增殖, 迁移, 上皮-间质转化, PI3K/Akt/NF-κB通路

Abstract: AIM: To study the inhibitory effect and mechanism of Jolkinolide B (JB) on the proliferation and metastasis of colon cancer HT-29 cells. METHODS: HT-29 cells were treated with different concentrations of JB, the cell proliferation rate was detected by MTT method, the cell clone formation rate was detected by plate cloning experiment, the cell cycle change was detected by flow cytometry, the cell migration ability was analyzed by wound healing assay, the cell invasion ability was studied by Transwell assay, E-cadherin, N-cadherin, vimentin, Snail1, Snail2, matrix metalloproteinase (MMP)-2 and MMP-9 protein expression levels were detected by immunofluorescence and Western blotting, and p-PI3K, PI3K, p-Akt, Akt, NF-κB P65and p-NF-κB P65 protein expression levels were detected by Western blotting. HT-29 cells were treated with 100 μg/L IGF-1 and 100 μg/L IGF-1+20 μmol/L JB, respectively. The expression of PI3K/Akt/NF-κB pathway related proteins was detected by Western blotting. RESULTS: JB inhibited the proliferation of HT-29 cells in a concentration-dependent manner, with an IC50 of 52.68 μmol/L for 24 hours; JB decreased the clone formation rate of HT-29 cells in a concentration-dependent manner (P<0.05); compared with the control group, the G0/G1 phase ratio of HT-29 cells treated with JB was significantly increased, while the S phase ratio was significantly decreased (P<0.05); JB could significantly inhibit the migration and invasion of HT-29 cells in vitro (P<0.05); the E-cadherin protein level of HT-29 cells treated with JB was increased, and the expression levels of N-cadherin, vimentin, Snail1, Snail2, MMP-2, MMP-9, p-PI3K, p-Akt, p-NF-κB P65 protein were significantly decreased (P<0.05). The expression of p-PI3K, p-Akt, p-NF-κB P65 in IGF-1+JB group was significantly lower than that in IGF-1 group (P<0.05). CONCLUSION: JB can inhibit the proliferation of HT-29 cells in vitro, induce cell arrest in the G0/G1 phase, inhibit the migration and invasion of HT-29, regulate the epithelial mesenchymal transition (EMT) and MMPs, and its mechanism may be related to the blocking of PI3K/Akt/NF-κB pathway.

Key words: Jolkinolide B, HT-29 cells, proliferation, migration, EMT, PI3K/Akt/NF-κB pathway

中图分类号:

R965.2

陈林俊, 陈文斌. 岩大戟内酯B通过阻断PI3K/Akt/NF-κB通路抑制结肠癌细胞的增殖和转移[J]. 中国临床药理学与治疗学, 2021, 26(3): 250-257.

CHEN Linjun, CHEN Wenbin. Jolkinolide B inhibits the proliferation and metastasis of colon cancer cells via blocking PI3K/Akt/NF-κB pathway[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(3): 250-257.

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岩大戟内酯B通过阻断PI3K/Akt/NF-κB通路抑制结肠癌细胞的增殖和转移

Jolkinolide B inhibits the proliferation and metastasis of colon cancer cells via blocking PI3K/Akt/NF-κB pathway

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