Study on the in vitro anti ovarian cancer effect and mechanism of quinazoline derivative(N111)  

作　　者：LI Yan HUANG Qiang HUANG Yin-jiu LIU Gang LIU Jian 

机构地区：[1]Department of Gynecology and Oncology,the First Affiliated Hospital of Bengbu Medical College,Bengbu 233099,China [2]College of Life Sciences,Bengbu Medical College,Bengbu 233030,China [3]School of Chemistry and Materials Science,Ludong University,Yantai 264025,China

出　　处：《Journal of Hainan Medical University》2023年第19期9-17,共9页海南医学院学报（英文版）

基　　金：Anhui Province University Natural Science Research Project (No.KJ2019A0363)。

摘　　要：Objective:To study the anti-ovarian cancer effect and mechanism of Quinazoline derivative(N111)in vitro;Method:Using an online database to predict the therapeutic targets of N111 for ovarian cancer,and conducting biological functional analysis of the therapeutic targets.The experiment was divided into N111 treatment group(N111 compound group),positive control group(cisplatin group),and negative control group(DMSO group);After grouping,MTT assay was used to detect cell proliferation;Morphological observation was used to observe changes in cell morphology;JC-1 and DCFH-DA probes were used to detect the changes of mitochondrial Membrane potential and intracellular reactive oxygen species;PI,Annexin V-FITC,and DAPI staining were used to detect cell cycle arrest and apoptosis;Clone formation experiments and scratch tests were conducted to detect the cell's ability to form clones and migrate;Western blot method was used to detect the expression level of related proteins.Result:The biological function research results show that the biological function of N111 anti ovarian cancer target protein suggests that the target function aggregates human diseases,inflammation,tumors,and other aspects.Compared with the control group,N111 has a significant inhibitory effect on the proliferation of ovarian cancer cells(IC50=14.62 mmol/L)(P<0.0001);In a concentration dependent manner,it inhibited the formation and migration of single cell colonies,and induced the disorder of mitochondrial Membrane potential,ROS and cell cycle arrest in S phase(P<0.0001);As the concentration of N111 treatment increased,the expression levels of Bcl2,Caspase 3,P-AKT,and SHIP2 decreased,while the expression levels of AKT remained unchanged.The expression levels of Bax and Cleared Caspase 3 increased(P<0.0001).Conclusion:Compound N111 inhibits SHIP2,promotes ROS level disorder,weakens the activation of AKT signaling pathway,and thus inhibits the proliferation,migration,and clone formation of tumor cell A2780,inducing cell apoptosis.

关 键 词：Quinazoline derivatives ANTI-TUMOR Apoptosis Mitochondrial membrane potential ROS 

分 类 号：R96[医药卫生—药理学]