中国临床药理学杂志

阿美替尼对非小细胞肺癌细胞增殖、侵袭、上皮间质转化和干性的作用

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谢友琴 ^1a , 高振 ^1b , 张亮 ^1a

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(5): 660-664

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (5) : 660 -664

阿美替尼对非小细胞肺癌细胞增殖、侵袭、上皮间质转化和干性的作用

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谢友琴^1a, 高振^1b, 张亮^1a

作者信息

^1a.南通市第一人民医院，肿瘤科，江苏南通 226000

^1b.南通市第一人民医院，放疗科，江苏南通 226000

通讯作者:

张亮，副主任医师 MP: 13706295558 E-mail: 346918235@qq.com

作者简介:

谢友琴（1991-），女，硕士研究生，主治医师，主要从事肺癌方面的研究

Effects of almonertinib on proliferation, invasion, epithelial mesenchymal transformation and stemness of non-small cell lung cancer cells

You-qin XIE^1a, Zhen GAO^1b, Liang ZHANG^1a

Affiliations

^1a.Department of Oncology, Nantong First People’s Hospital, Nantong 226000, Jiangsu Province, China

^1b.Department of Radiotherapy, Nantong First People’s Hospital, Nantong 226000, Jiangsu Province, China

出版时间: 2025-03-17 doi: 10.13699/j.cnki.1001-6821.2025.05.012

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摘要

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目的

研究阿美替尼通过调控微小核糖核酸-22（miR-22）靶向泛素结合酶E2O（UBE2O）对非小细胞肺癌（NSCLC）细胞的增殖、侵袭、上皮间质转化和干性的影响。

方法

将人肺腺癌细胞系NCI-H1975随机分为对照组（无任何处理正常培养）、中剂量组（4 μmol·L^-1阿美替尼处理）、抑制药阴性对照（转染NC inhibitor）组（4 μmol·L^-1阿美替尼+miR-22抑制药阴性对照处理）、miR-22抑制药（miR-22 inhibitor）组（4 μmol·L^-1阿美替尼+miR-22抑制药处理）、miR-22 inhibitor+短发卡阴性对照（sh-NC）组（4 μmol·L^-1阿美替尼+miR-22抑制药+短发卡阴性对照处理）、miR-22 inhibitor+短发卡UBE2O（sh-UBE2O）组（4 μmol·L^-1阿美替尼+miR-22抑制药+短发卡UBE2O处理）。用实时荧光定量聚合酶链反应（qRT-PCR）检测miR-22表达，用蛋白质印迹法检测八聚体结合转录因子4（OCT4）、性别决定区域Y盒基因2（SOX2）和Nanog同源框的表达水平，用5-乙炔基-2′-脱氧尿嘧啶核苷（EdU）实验检测细胞增殖率，用Transwell实验检测细胞侵袭能力。

结果

对照组和中剂量组的miR-22相对表达水平分别为1.00±0.16和2.07±0.34；对照组、中剂量组、NC inhibitor组和miR-22 inhibitor组的OCT4蛋白相对表达水平分别为1.00±0.16、0.63±0.09、0.67±0.08和0.94±0.12，SOX2蛋白相对表达水平分别为1.00±0.14、0.48±0.06、0.54±0.07和0.81±0.11，Nanog蛋白相对表达水平分别为1.00±0.18、0.45±0.08、0.52±0.11和0.89±0.15。对照组、中剂量组、NC inhibitor组、miR-22 inhibitor组、miR-22 inhibitor+sh-NC组和miR-22 inhibitor+sh-UBE2O组的细胞增殖率分别为（87.29±10.73）%、（41.65±7.82）%、（48.47±6.54）%、（79.31±10.26）%、（84.50±11.98）%和（36.82±6.79）%，细胞侵袭数目分别为（156.92±24.81）、（72.53±9.06）、（64.41±10.75）、（143.27±26.19）、（137.58±21.46）和（75.23±11.94）个。对照组的上述指标与中剂量组，NC inhibitor组的上述指标与miR-22 inhibitor组，miR-22 inhibitor+sh-NC组的上述指标与miR-22 inhibitor+sh-UBE2O组比较，在统计学上差异均有统计学意义（均P<0.05）。

结论

阿美替尼能抑制非小细胞肺癌NCI-H1975细胞的增殖和侵袭，可能是通过调控miR-22靶向UBE2O实现的。

关键词

阿美替尼 / 微小核糖核酸-22 / 泛素结合酶E2O / 非小细胞肺癌 / 增殖 / 侵袭 / 上皮间质转化 / 干性标志物

Abstract

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Objective

To investigate the effects of almonertinib on the proliferation, invasion, epithelial-mesenchymal transition (EMT), and stemness of non-small-cell lung cancer (NSCLC) cells by regulating microRNA-22 (miR-22) targeting ubiquitin-conjugating enzyme E2O (UBE2O).

Methods

Human lung adenocarcinoma cell line NCI-H1975 was randomly divided into control group (normal culture with no treatment), medium-dose group (4 μmol·L^-1 almonertinib), inhibitor negative control (NC inhibitor) group (4 μmol·L^-1 almonertinib + miR-22 inhibition negative control), miR-22 inhibitor group (4 μmol·L^-1 almonertinib + miR-22 inhibition), miR-22 inhibitor+short hairpin negative control (sh-NC) group (4 μmol·L^-1 almonertinib + miR-22 inhibition + short hairpin negative control), and miR-22 inhibitor+short hairpin UBE2O (sh-UBE2O) group (4 μmol·L^-1 almonertinib + miR-22 inhibition + short hairpin UBE2O). The expression of miR-22 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) ; Western blot analysis was performed to detect the expression of octamer-binding transcription factor 4 (OCT4), SRY-Box transcription factor 2 (SOX2), and Nanog; the cell proliferation rate was assessed using the 5-ethynyl-2-deoxyuridine (EdU) assay; and Transwell assays were conducted to evaluate cell invasion ability.

Results

The expression levels of miR-22 in the control group, medium-dose group were 1.00±0.16, 2.07±0.34. The expression levels of OCT4 in the control group, medium-dose group, NC inhibitor group, and miR-22 inhibitor group were 1.00±0.16, 0.63±0.09, 0.67±0.08 and 0.94±0.12, respectively; SOX2 expression levels were 1.00±0.14, 0.48±0.06, 0.54±0.07 and 0.81±0.11; and Nanog expression levels were 1.00±0.18, 0.45±0.08, 0.52±0.11 and 0.89±0.15. The cell proliferation rates in the control group, medium-dose group, NC inhibitor group, miR-22 inhibitor group, miR-22 inhibitor+sh-NC group, and miR-22 inhibitor+sh-UBE2O group were (87.29±10.73)%, (41.65±7.82)%, (48.47±6.54)%, (79.31±10.26)%, (84.50±11.98)% and (36.82±6.79)%, respectively. The numbers of invading cells were (156.92±24.81), (72.53±9.06), (64.41±10.75), (143.27±26.19), (137.58±21.46) and (75.23±11.94), respectively. Compared between the control group and medium-dose group, NC inhibitor and miR-22 inhibitor groups, as well as miR-22 inhibitor+sh-NC and miR-22 inhibitor+sh-UBE2O groups showed statistically significant differences (all P<0.05).

Conclusion

Almonertinib can inhibit the proliferation and invasion of NSCLC NCI-H1975 cells, likely by regulating miR-22 to target UBE2O.

Key words

almonertinib / microRNA-22 / ubiquitin conjugating enzyme E2O / non-small cell lung cancer / proliferation / invasion / epithelial-mesenchymal transition / stemness markers

引用本文

谢友琴, 高振, 张亮. 阿美替尼对非小细胞肺癌细胞增殖、侵袭、上皮间质转化和干性的作用. 中国临床药理学杂志, 2025 , 41 (5) : 660 -664 . DOI: 10.13699/j.cnki.1001-6821.2025.05.012

You-qin XIE, Zhen GAO, Liang ZHANG. Effects of almonertinib on proliferation, invasion, epithelial mesenchymal transformation and stemness of non-small cell lung cancer cells[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (5) : 660 -664 . DOI: 10.13699/j.cnki.1001-6821.2025.05.012

基金

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南通市卫生健康委员会科研基金资助项目(MS2023030)

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2025年第41卷第5期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2025.05.012

接收时间：2024-10-22
首发时间：2026-08-04
出版时间：2025-03-17

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收稿日期：2024-10-22

基金

南通市卫生健康委员会科研基金资助项目(MS2023030)

作者信息

^1a.南通市第一人民医院，肿瘤科，江苏南通 226000

^1b.南通市第一人民医院，放疗科，江苏南通 226000

通讯作者:

张亮，副主任医师 MP: 13706295558 E-mail: 346918235@qq.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.05.012

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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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