基于转录组测序探讨β-榄香烯联合奥希替尼对肺癌细胞敏感性研究  

Research on the sensitivity ofβ-elemene combined with osimertinib to lung cancer cells based on transcriptome sequencing

作　　者：刘格戈 姜晓天 LIU Gege;JIANG Xiaotian(Affiliated Hospital of Changchun University of Chinese Medicine,Changchun 130021,China)

机构地区：[1]长春中医药大学附属医院,长春130021

出　　处：《吉林中医药》2024年第9期1085-1089,共5页Jilin Journal of Chinese Medicine

基　　金：吉林省教育厅科学技术研究项目(JJKH20210983KJ)。

摘　　要：目的探讨β-榄香烯增加奥希替尼对肺癌细胞敏感性的体外药理作用和机制。方法通过细胞增殖实验测试不同浓度的β-榄香烯、奥希替尼及联合用药组的肺癌细胞存活率。划痕实验、细胞侵袭实验和流式细胞术对β-榄香烯、奥希替尼及联合用药组肺癌细胞抑制侵袭迁移能力和诱导凋亡能力进行检测。随后应用转录组测序分析β-榄香烯联合奥希替尼对肺癌细胞敏感性的机制。结果β-榄香烯在50、100、200、400μg/mL与奥希替尼1.25、2.5、5、10μg/mL浓度梯度配对组合中均抑制肺癌细胞存活率(P<0.05)。在β-榄香烯100μg/mL,奥希替尼2.5μg/mL及联合用药组中,联合用药组抑制肺癌细胞迁移和侵袭能力(P<0.05),并诱导肺癌细胞凋亡。对转录组测序分析显示,β-榄香烯联合奥希替尼对比奥希替尼干预后PC9细胞,MAPK通路和细胞凋亡相关生物过程被富集。结论β-榄香烯通过MAPK通路增加了奥希替尼对肺癌细胞敏感性,促进了细胞凋亡。Objective To investigate the in vitro pharmacological effects and mechanisms ofβ-elemene on the enhancement of osimertinib responsiveness to lung cancer cells.Methods The lung cancer cell viability was assessed in varying dosages ofβ-elemene,osimertinib,and their combinations through cell proliferation experiments.Wound healing,cell invasion test andflow cytometry were used to detect the ability of lung cancer cells inβ-elemene,osimertinib and combination groups to inhibit invasion and migration and induce apoptosis.Subsequently,transcriptome sequencing analysis was applied to explore the mechanism by whichβ-elemene increases its sensitivity to osimertinib.Results The survival of lung cancer cells was markedly reduced when subjected toβ-elemene at dosages of 50,100,200,and 400μg/mL in conjunction with osimertinib in a gradient of concentrations including 2.5,5,10,and 20μM(P<0.05).Furthermore,when lung cancer cells were treated with a mixture ofβ-elemene at 100μg/mL and osimertinib at 5μM,the amalgamated treatment notably suppressed cell migration and invasion(P<0.05),and also prompted apoptosis.The MAPK pathway and apoptosis-related biological processes were enriched in the transcriptome sequencing analysis of PC9 lung cancer cells.Conclusionβ-elemene increases the sensitivity of osimertinib to lung cancer cells through the MAPK pathway and promotes cell senescence and apoptosis.

关 键 词：Β-榄香烯 奥希替尼 肺癌 MAPK通路 

分 类 号：R245[医药卫生—针灸推拿学]