[Aumolertinib combined with anlotinib inhibits proliferation of non-small cell lung cancer cells by down-regulating the PI3K/AKT pathway].

Q3 Medicine

南方医科大学学报杂志 Pub Date : 2024-10-20 DOI:10.12122/j.issn.1673-4254.2024.10.15

Y Yang, X Liu, W Liu, X Zhou, Z Zhang, Y Hu, P Liu, X Li, H Liu, S Li

{"title":"[Aumolertinib combined with anlotinib inhibits proliferation of non-small cell lung cancer cells by down-regulating the PI3K/AKT pathway].","authors":"Y Yang, X Liu, W Liu, X Zhou, Z Zhang, Y Hu, P Liu, X Li, H Liu, S Li","doi":"10.12122/j.issn.1673-4254.2024.10.15","DOIUrl":null,"url":null,"abstract":"Objective: To investigate the inhibitory effect of aumolertinib combined with anlotinib on proliferation of non-small cell lung cancer (NSCLC) cells.Methods: CCK-8 assay, colony formation assay, and flow cytometry were used to assess the effect of different concentrations of aumolertinib or anlotinib on proliferation, survival, and apoptosis of PC-9 and HCC827 cells, and their synergistic effect was evaluated using the SynergyFinder model. In PC-9 and HCC827 cells treated with aumolertinib combined with anlotinib, the changes in cell invasion and migration abilities were assessed with Transwell assay, and the expressions of apoptosis- and invasion/migration-related proteins (Bax, Bcl-2, E-cadherin, vimentin, MMP2, and MMP9) and the key PI3K-Akt pathway proteins were detected using Western blotting.Results: In PC-9 cells, the IC50 of aumolertinib and anlotinib was 1.701 μmol/L and 4.979 μmol/L, respectively, with a synergy score (ZIP) of 19.112; in HCC827 cells, their IC50 was 2.961 μmol/L and 7.934 μmol/L, respectively, with a ZIP of 12.325. Compared with aumolertinib and anlotinib used alone, their combined treatment more strongly inhibited the proliferation and survival, enhanced apoptosis and suppressed invasion and migration abilities of PC-9 and HCC827 cells. Western blotting showed that in both PC-9 and HCC827 cells, the combined treatment significantly upregulated the expressions of E-cadherin and Bax proteins, downregulated the expressions of Bcl-2, vimentin, MMP2, and MMP9 proteins, and reduced phosphorylation levels of PI3K and Akt.Conclusion: Aumolertinib combined with anlotinib can effectively inhibit NSCLC cell proliferation by downregulating the PI3K-Akt pathway, suggesting a potentially new option for NSCLC treatment.","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"44 10","pages":"1965-1975"},"PeriodicalIF":0.0000,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526449/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"南方医科大学学报杂志","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.12122/j.issn.1673-4254.2024.10.15","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: To investigate the inhibitory effect of aumolertinib combined with anlotinib on proliferation of non-small cell lung cancer (NSCLC) cells.

Methods: CCK-8 assay, colony formation assay, and flow cytometry were used to assess the effect of different concentrations of aumolertinib or anlotinib on proliferation, survival, and apoptosis of PC-9 and HCC827 cells, and their synergistic effect was evaluated using the SynergyFinder model. In PC-9 and HCC827 cells treated with aumolertinib combined with anlotinib, the changes in cell invasion and migration abilities were assessed with Transwell assay, and the expressions of apoptosis- and invasion/migration-related proteins (Bax, Bcl-2, E-cadherin, vimentin, MMP2, and MMP9) and the key PI3K-Akt pathway proteins were detected using Western blotting.

Results: In PC-9 cells, the IC50 of aumolertinib and anlotinib was 1.701 μmol/L and 4.979 μmol/L, respectively, with a synergy score (ZIP) of 19.112; in HCC827 cells, their IC50 was 2.961 μmol/L and 7.934 μmol/L, respectively, with a ZIP of 12.325. Compared with aumolertinib and anlotinib used alone, their combined treatment more strongly inhibited the proliferation and survival, enhanced apoptosis and suppressed invasion and migration abilities of PC-9 and HCC827 cells. Western blotting showed that in both PC-9 and HCC827 cells, the combined treatment significantly upregulated the expressions of E-cadherin and Bax proteins, downregulated the expressions of Bcl-2, vimentin, MMP2, and MMP9 proteins, and reduced phosphorylation levels of PI3K and Akt.

Conclusion: Aumolertinib combined with anlotinib can effectively inhibit NSCLC cell proliferation by downregulating the PI3K-Akt pathway, suggesting a potentially new option for NSCLC treatment.

查看原文本刊更多论文

[奥莫拉替尼联合安罗替尼通过下调 PI3K/AKT 通路抑制非小细胞肺癌细胞的增殖】。］

目的：研究奥莫特尼联合安罗替尼对非小肺癌细胞增殖的抑制作用：研究奥美替尼联合安罗替尼对非小细胞肺癌（NSCLC）细胞增殖的抑制作用：方法：采用CCK-8试验、集落形成试验和流式细胞术评估不同浓度的奥美替尼或安罗替尼对PC-9和HCC827细胞增殖、存活和凋亡的影响，并使用SynergyFinder模型评估它们的协同效应。在PC-9和HCC827细胞中使用奥莫利替尼联合安罗替尼治疗，用Transwell试验评估细胞侵袭和迁移能力的变化，并用Western印迹法检测细胞凋亡和侵袭/迁移相关蛋白（Bax、Bcl-2、E-adherin、vimentin、MMP2和MMP9）以及PI3K-Akt通路关键蛋白的表达：在PC-9细胞中，奥莫勒替尼和安罗替尼的IC50分别为1.701 μmol/L和4.979 μmol/L，协同作用得分（ZIP）为19.112；在HCC827细胞中，它们的IC50分别为2.961 μmol/L和7.934 μmol/L，协同作用得分（ZIP）为12.325。与单独使用奥美替尼和安罗替尼相比，它们联合使用能更强地抑制PC-9和HCC827细胞的增殖和存活，增强其凋亡，抑制其侵袭和迁移能力。Western印迹显示，在PC-9和HCC827细胞中，联合治疗可显著上调E-cadherin和Bax蛋白的表达，下调Bcl-2、波形蛋白、MMP2和MMP9蛋白的表达，降低PI3K和Akt的磷酸化水平：结论：奥莫乐替尼联合安罗替尼可通过下调PI3K-Akt通路有效抑制NSCLC细胞增殖，有望成为NSCLC治疗的新选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊