|Table of Contents|

The effect of orlistat combined with almonertinib on the proliferation,migration and invasion of lung adenocarcinoma H1975 cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 22
Page:
4245-4249
Research Field:
Publishing date:

Info

Title:
The effect of orlistat combined with almonertinib on the proliferation,migration and invasion of lung adenocarcinoma H1975 cells
Author(s):
CHEN Tao; LIU Dan; DENG Shukai
Department of Respiratory and Critical Care Medicine,Affiliated Hospital of Southwest Medical University,Sichuan Luzhou 646000,China.
Keywords:
orlistat; almonertinib; lung adenocarcinoma cells; EGFR-AKT signalling pathway; FASN; epithelial mesenchymal transformation
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2024.22.005
Abstract:
Objective:To investigate the effect of orlistat (Orli) combined with almonertinib (Alm) on the proliferation,migration and invasion of lung adenocarcinoma H1975 cells and its mechanism.Methods:After treating lung adenocarcinoma H1975 cells with different concentrations of Orli and Alm alone and in combination,cell proliferation activity was detected by CCK-8 assay,and the half inhibitory concentration (IC50) and combination index (CI) of Alm were calculated.Transwell assay was performed to detect the ability of the cells to migrate and invade.The expression levels of cellular FASN proteins,EGFR-AKT signalling pathway-related proteins,epithelial-mesenchymal transition factors E-cadherin and N-cadherin were detected by Western blotting.Results:Compared with the control group,the proliferative activity of H1975 cells could be inhibited to a certain extent after treatment with different concentrations of Orli,Alm and the combination of drugs,and the inhibition of the proliferative activity of H1975 cells by low-dose Orli combined with Alm had a synergistic effect (CI<1).In addition,the number of cell migration and invasion was significantly reduced in the low-dose combination group compared with the control group and each single-drug group (P＜0.05).The expression levels of EGFR,p-EGFR and p-AKT,and FASN proteins in the cells of the low-dose combination group were significantly reduced compared with those of all groups (P＜0.05)，and the expression levels of the epithelial-mesenchymal transition factor E-cadherin were up-regulated,and the expression levels of N-cadherin were down-regulated (P＜0.05).Conclusion:Orli combined with Alm synergistically inhibited the proliferation,migration and invasion of H1975 cells,and its mechanism of action may be related to the down-regulation of FASN protein expression and the inhibition of phosphorylation of EGFR pathway signalling molecules.

References:

［1］ CHEN P,LIU Y,WEN Y,et al.Non-small cell lung cancer in China［J］.Cancer Commun (Lond),2022,42(10):937-970.
［2］ KIM ES,MELOSKY B,PARK K,et al.EGFR tyrosine kinase inhibitors for EGFR mutation-positive non-small-cell lung cancer:outcomes in Asian populations［J］.Future Oncol,2021,17(18):2395-2408.
［3］ SHIRLEY M,KEAM SJ.Aumolertinib:A review in non-small cell lung cancer［J］.Drugs,2022,82(5):577-584.
［4］ FHU CW,ALI A.Fatty acid synthase:an emerging target in cancer［J］.Molecules,2020,25(17):3935.
［5］ LUNG J,HUNG MS,WANG TY,et al.Lipid droplets in lung cancers are crucial for the cell growth and starvation survival［J］.Int J Mol Sci,2022,23(20):12533.
［6］ SCHCOLNIK-CABRERA A,CHAVEZ-BLANCO A,DOMINGUEZ-GOMEZ G,et al.Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy［J］.Expert Opin Investig Drugs,2018,27(5):475-489.
［7］ GE X,ZHANG Y,HUANG F,et al.EGFR tyrosine kinase inhibitor Almonertinib induces apoptosis and autophagy mediated by reactive oxygen species in non-small cell lung cancer cells［J］.Hum Exp Toxicol,2021,40(12_suppl):S49-S62.
［8］ LU S,DONG X,JIAN H,et al.AENEAS:A randomized phase III trial of Aumolertinib versus Gefitinib as first-line therapy for locally advanced or metastatic non-small-cell lung cancer with EGFR exon 19 deletion or L858R mutations［J］.J Clin Oncol,2022,40(27):3162-3171.
［9］ 崔久嵬,段建春,任胜祥,等.三代EGFR-TKI在EGFR突变NSCLC治疗中应用的专家共识（2022年版）［J］.中国肺癌杂志,2022,25(09):627-641. CUI JW,DUAN JC,REN SX,et al.Consensus on application of third-generation EGFR-TKI in EGFR mutated NSCLC［J］.Chinese Journal of Lung Cancer,2022,25(09):627-641.
［10］ BAYAT MOKHTARI R,HOMAYOUNI TS,BALUCH N,et al.Combination therapy in combating cancer［J］.Oncotarget,2017,8(23):38022-38043.
［11］ 吴晶,周娟,苏春霞.肺癌脂肪酸代谢重编程的研究进展［J］.中国癌症杂志,2023,33(05):517-526. WU J,ZHOU J,SU CX.Advances in fatty acid metabolism reprogramming of lung cancer［J］.China Oncology,2023,33(05):517-526.
［12］ BUTLER LM,PERONE Y,DEHAIRS J,et al.Lipids and cancer:Emerging roles in pathogenesis,diagnosis and therapeutic intervention［J］.Adv Drug Deliv Rev,2020,159:245-293.
［13］ BOLLU LR,KATREDDY RR,BLESSING AM,et al.Intracellular activation of EGFR by fatty acid synthase dependent palmitoylation［J］.Oncotarget,2015,6(33):34992-5003.
［14］ ALI A,LEVANTINI E,TEO JT,et al.Fatty acid synthase mediates EGFR palmitoylation in EGFR mutated non-small cell lung cancer［J］.EMBO Mol Med,2018,10(3):e8313.
［15］ TYAN YS,LEE YP,CHUANG HY,et al.Effects of orlistat combined with enzalutamide and castration through inhibition of fatty acid synthase in a PC3 tumor-bearing mouse model［J］.Biosci Rep,2021,41(5):BSR20204203.
［16］ TADROS S,SHUKLA SK,KING RJ,et al.De novo lipid synthesis facilitates gemcitabine resistance through endoplasmic reticulum stress in pancreatic cancer［J］.Cancer Res,2017,77(20):5503-5517.
［17］ POLONIO-ALCALAE,PORTA R,RUIZ-MARTINEZ S,et al.AZ12756122,a novel fatty acid synthase inhibitor,decreases resistance features in EGFR-TKI resistant EGFR-mutated NSCLC cell models［J］.Biomed Pharmacother,2022,156:113942.
［18］ LI F,SONG QZ,ZHANG YF,et al.Identifying the EMT-related signature to stratify prognosis and evaluate the tumor microenvironment in lung adenocarcinoma［J］.Front Genet,2022,13:1008416.
［19］谢慧静,南欣荣.口腔鳞状细胞癌中上皮-间充质转化相关影响因素的研究进展［J］.现代肿瘤医学，2022,30(10):1890-1893. XIE HJ,NAN XR.Factors influencing epithelial-mesenchymal transition in oral squamous cell carcinoma［J］.Modern Oncology,2022,30(10):1890-1893.
［20］殷文博,王子安.癌胚抗原联合空腹血糖水平检测评估晚期胃癌预后的价值分析［J］.现代肿瘤医学，2023,31(2)：282-286. YIN WB,WANG ZA.The value of level detection of carcinoembryonic antigen combined with fasting plasma glucose for evaluating the prognosis of advanced gastric cancer［J］.Modern Oncology,2023,31(2)：282-286.
［21］ ATIYA HI,GORECKI G,GARCIA GL,et al.Stromal-modulated epithelial-to-mesenchymal transition in cancer cells［J］.Biomolecules,2023,13(11):1604.
［22］ 余方方,李巨元,黄健,等.靶向沉默脂肪酸合酶FASN基因对食管癌细胞失巢凋亡及转移水平的调控作用［J］.现代肿瘤医学,2023,31(15):2809-2815. YU FF,LI JY,HUANG J,et al.Effects of targeted silencing fatty acid synthase FASN gene on apoptosis and metastasis level of esophageal cancer cells in lost nests［J］.Modern Oncology,2023,31(15):2809-2815.

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