中国临床药理学杂志

楝酰胺通过调控细胞自噬影响乳腺癌耐药细胞株MCF-7/PTX对紫杉醇耐药的研究

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张立柱 ^1a , 韩长辉 ^1b , 范焕芳 ^1b , 张洋 ² , 赵康超 ³

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(11): 1569-1574

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (11) : 1569 -1574

楝酰胺通过调控细胞自噬影响乳腺癌耐药细胞株MCF-7/PTX对紫杉醇耐药的研究

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张立柱^1a, 韩长辉^1b, 范焕芳^1b, 张洋², 赵康超³

作者信息

^1a.河北省中医院，外一科，河北石家庄 050011

^1b.河北省中医院，肿瘤二科，河北石家庄 050011

^2.南宫市人民医院肿瘤科，河北邢台 055750

^3.河北中医学院中西医结合学院，河北石家庄 050020

通讯作者:

范焕芳，教授，主任医师 MP: 15690318188 E-mail: fhf701024@163.com

作者简介:

张立柱（1973-），男，副主任医师，主要从事乳腺癌临床及基础方向的研究

Rocaglamide reverses paclitaxel resistance of drug resistant breast cancer cell line MCF-7/PTX by regulating cell autophagy

Li-zhu ZHANG^1a, Chang-hui HAN^1b, Huan-fang FAN^1b, Yang ZHANG², Kang-chao ZHAO³

Affiliations

^1a.Department of Surgery Ⅰ, Hebei Province Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, Hebei Province, China

^1b.Department of Oncology Ⅱ, Hebei Province Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, Hebei Province, China

^2.Department of Oncology, Nangong People’s Hospital, Xingtai 055750, Hebei Province, China

^3.Institute of Integrated Traditional and Western Medicine, Hebei College of Traditional Chinese Medicine, Shijiazhuang 050020, Hebei Province, China

出版时间: 2025-06-17 doi: 10.13699/j.cnki.1001-6821.2025.11.013

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摘要

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目的

探讨楝酰胺（Roc-A）对乳腺癌MCF-7/PTX细胞株紫杉醇（PTX）耐药的影响及其作用机制。

方法

以乳腺癌MCF-7细胞为研究对象，用PTX低浓度加量持续诱导法获得PTX耐药株MCF-7/PTX，用四甲基偶氮唑蓝（MTT）法测定MCF-7/PTX细胞株的耐药指数及Roc-A对MCF-7/PTX细胞株增殖活性的影响及耐药逆转倍数。将MCF-7/PTX细胞株分为对照组（正常培养的细胞）、PTX组（40.8 nmol·L^-1 PTX）、PTX+Roc-A-L组（40.8 nmol·L^-1 PTX+25 nmol·L^-1Roc-A）、PTX+Roc-A-M组（40.8 nmol·L^-1PTX+50 nmol·L^-1 Roc-A）和PTX+Roc-A-H组（40.8 nmol·L^-1 PTX+100 nmol·L^-1 Roc-A）。用流式细胞术检测细胞凋亡情况，用免疫荧光法检测细胞自噬相关蛋白LC3的相对表达水平，用蛋白质印迹法检测细胞凋亡相关蛋白B细胞淋巴瘤-2相关X蛋白（Bax）和自噬相关蛋白自噬微管相关蛋白轻链3（LC3）的相对表达水平。

结果

成功构建乳腺癌PTX耐药细胞株MCF-7/PTX，耐药指数为5.49；Roc-A可呈浓度依赖性抑制MCF-7/PTX细胞株增殖活性，而不同浓度（25、50、100 nmol·L^-1）Roc-A对MCF-7/PTX细胞株PTX耐药性的逆转倍数分别为1.57、2.68和6.16。对照组、PTX组、PTX+Roc-A-L组、PTX+Roc-A-M组和PTX+Roc-A-H组的细胞凋亡率分别为（4.75±2.10）%、（21.79±3.61）%、（32.54±3.43）%、（39.82±3.26）%和（55.61±4.22）%，LC3荧光相对表达水平分别为1.00±0.08、0.77±0.06、0.60±0.06、0.41±0.04和0.26±0.03，Bax蛋白相对表达水平分别为0.12±0.04、0.25±0.09、0.48±0.10、0.86±0.12和1.10±0.13，LC3Ⅱ/LC3Ⅰ蛋白比值分别为6.52±0.27、3.75±0.23、1.76±0.17、1.31±0.10和1.02±0.06。PTX组、PTX+Roc-A-M组、PTX+Roc-A-L组、PTX+Roc-A-H组的上述指标与对照组比较，在统计学上差异均有统计学意义（均P<0.05）；PTX+Roc-A-M组、PTX+Roc-A-L组、PTX+Roc-A-H组的上述指标与PTX组比较，在统计学上差异均有统计学意义（均P<0.05），并呈剂量依赖性。

结论

Roc-A能逆转乳腺癌耐药细胞株MCF-7/PTX对PTX的耐药性，其机制可能与降低自噬有关。

关键词

楝酰胺 / 紫杉醇 / 乳腺癌耐药株 / 细胞凋亡 / 自噬

Abstract

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Objective

To investigate the effect of Rocaglamide (Roc-A) on paclitaxel (PTX) resistance in breast cancer MCF-7/PTX cell line and its mechanism.

Methods

With breast cancer MCF-7 cells as the research object, PTX resistant MCF-7/PTX cell line was obtained by continuous induction with low concentration of PTX. Methyl thiazolyl tetrazolium (MTT) method was used to determine the drug resistance index of MCF-7/PTX cell line, the effect of Roc-A on the proliferation activity of MCF-7/PTX cell line and the drug resistance reversal multiple. MCF-7/PTX cell lines were divided into control group (normal cultured cells), PTX group (40.8 nmol·L^-1 PTX), PTX+Roc-A-L group (40.8 nmol·L^-1 PTX+25 nmol·L^-1 Roc-A), PTX+Roc-A-M group (40.8 nmol·L^-1 PTX+50 nmol·L^-1 Roc-A) and PTX+Roc-A-H group (40.8 nmol·L^-1 PTX+100 nmol·L^-1 Roc-A). The apoptosis level of each group was detected by flow cytometry; the relative expression levels of cell autophagy related protein LC3 were detected by immunofluorescence assay; Western blotting was used to detect the relative expression levels of cell apoptosis related proteins, such as B cell lymphoma-2 associated X protein (Bax) and autophagy associated protein autophagy microtubule associated protein light chains 3 (LC3).

Results

The PTX resistant cell line MCF-7/PTX of breast cancer was successfully constructed with a drug resistance index of 5.49; Roc-A could inhibit the proliferation activity of MCF-7/PTX cell lines in a concentration dependent manner, while the reversal multiples of PTX resistance of MCF-7/PTX cell lines to Roc-A at different concentrations (25, 50, 100 nmol·L^-1) were 1.57, 2.68 and 6.16, respectively. The apoptosis rates of the control group, PTX group, PTX+Roc-A-L group, PTX+Roc-A-M group and PTX+Roc-A-H group were (4.75±2.10)%, (21.79±3.61)%, (32.54±3.43)%, (39.82±3.26)% and (55.61±4.22)%, respectively; the relative expression levels of LC3 fluorescence were 1.00±0.08, 0.77±0.06, 0.60±0.06, 0.41±0.04 and 0.26±0.03, respectively; the relative expression levels of Bax protein were 0.12±0.04, 0.25±0.09, 0.48±0.10, 0.86±0.12 and 1.10±0.13, respectively; the LC3Ⅱ/LC3Ⅰ protein ratio were 6.52±0.27, 3.75±0.23, 1.76±0.17, 1.31±0.10 and 1.02±0.06, respectively. Compared with the control group, the PTX group, PTX+Roc-A-L group, PTX+Roc-A-M group, PTX+Roc-A-H group showed statistically significant differences in the above indicators (all P<0.05); the above indicators in the PTX+Roc-A-L group, PTX+Roc-A-M group and PTX+Roc-A-H group were compared with those in the PTX group, and the differences were statistically significant (all P<0.05), showing a dose-dependent relationship.

Conclusion

Roc-A can reverse the resistance of breast cancer drug resistant cell line MCF-7/PTX to PTX, and the mechanism may be related to the reduction of autophagy.

Key words

rocaglamidel / paclitaxel / resistant breast cancer cell line / apoptosis / autophagy

引用本文

张立柱, 韩长辉, 范焕芳, 张洋, 赵康超. 楝酰胺通过调控细胞自噬影响乳腺癌耐药细胞株MCF-7/PTX对紫杉醇耐药的研究. 中国临床药理学杂志, 2025 , 41 (11) : 1569 -1574 . DOI: 10.13699/j.cnki.1001-6821.2025.11.013

Li-zhu ZHANG, Chang-hui HAN, Huan-fang FAN, Yang ZHANG, Kang-chao ZHAO. Rocaglamide reverses paclitaxel resistance of drug resistant breast cancer cell line MCF-7/PTX by regulating cell autophagy[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (11) : 1569 -1574 . DOI: 10.13699/j.cnki.1001-6821.2025.11.013

基金

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河北省中医药管理局科研计划基金资助项目(2021024)

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2025年第41卷第11期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2025.11.013

接收时间：2024-12-26
首发时间：2026-08-04
出版时间：2025-06-17

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收稿日期：2024-12-26

基金

河北省中医药管理局科研计划基金资助项目(2021024)

作者信息

^1a.河北省中医院，外一科，河北石家庄 050011

^1b.河北省中医院，肿瘤二科，河北石家庄 050011

^2.南宫市人民医院肿瘤科，河北邢台 055750

^3.河北中医学院中西医结合学院，河北石家庄 050020

通讯作者:

范焕芳，教授，主任医师 MP: 15690318188 E-mail: fhf701024@163.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.11.013

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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