4-乙氧基-2-羟基-6-甲基苯甲酸体外抗肿瘤作用及与顺铂联合作用研究  

In Vitro Anticancer Effects of 4-Ethoxy-2-hydroxy-6-methyl Benzoic Acid and Its Combinative Anticancer Effects with Cis-DDP

作　　者：王子睿[1] 贺小琼[1] 姚乾[2] 王静[1] 贺云发 胡松杉 

机构地区：[1]昆明医科大学公共卫生学院,云南昆明650500 [2]昆明医科大学第三附属医院云南省肿瘤研究所,云南昆明650118

出　　处：《昆明医科大学学报》2014年第9期4-8,共5页Journal of Kunming Medical University

基　　金：国家自然科学基金资助项目(30960437);云南省自然科学基金资助项目(2009FXL001)

摘　　要：目的研究4-乙氧基-2-羟基-6-甲基苯甲酸(以下简称D6B2)对多株人体肿瘤细胞体外抗肿瘤作用的剂量-效应和时间-效应关系,发现敏感的肿瘤细胞株,观察该化合物与临床抗癌药物是否具有体外联合抗肿瘤作用,以及作用形式和强度.方法采用体外抗肿瘤实验,研究不同浓度的D6B2对人鼻咽癌细胞株CNE、人肝癌细胞株Hep G2、人子宫颈癌细胞株HeLa、人胆管癌细胞株QBC939和人白血病细胞株K562的体外抑制作用的剂量-效应关系,进一步观察该化合物对HeLa细胞体外抑制作用的时间-效应关系,以及其与顺铂是否具有联合抗肿瘤作用.结果 D6B2在浓度为25μM、50μM、100μM、150μM、200μM时对CNE细胞的抑制率分别为24.94%、42.11%、65.74%、70.22%、73.11%,IC50为66.9μM;对Hep G2细胞的抑制率分别为23.15%、54.56%、62.95%、70.14%、75.18%,IC50为60.98μM;对HeLa细胞的抑制率分别为31.34%、60.76%、78.43%、85.78%、90.75%,IC50为40.7μM;对QBC939细胞的抑制率分别为5.97%、12.05%、28.44%、35.28%、51.31%,IC50为197.07μM;对K562细胞的抑制率分别为18.20%、35.48%、46.76%、58.44%、57.32%,IC50为120.06μM.D6B2对HeLa细胞的24 h抑制率分别为7.96%、9.56%、10.98%、14.00%、17.33%,48 h抑制率分别为10.62%、25.96%、47.63%、48.24%、49.03%,72 h抑制率分别为18.08%、53.68%、85.55%、87.86%、82.07%.D6B2在25μM、50μM、100μM剂量下与10μM的DDP联合用药,3组的CDI值分别为0.039、0.019和0.014.结论 D6B2对CNE、Hep G2、HeLa、QBC939和K562细胞均有显著的体外抗肿瘤作用,存在明显的剂量-效应关系,人子宫颈癌细胞株HeLa对其最为敏感.D6B2对HeLa的体外抑制作用具有时间-效应关系.D6B2与临床抗癌药物顺铂具有显著的体外协同抗肿瘤作用.Objective To investigate the in vitro anticancer effects of 4-ethoxy-2-hydroxy-6-methyl benzoic acid（D6B2） and its combinative anticancer effects with clinical anticancer drug cis-DDP. Methods Human cancer cell lines CNE,Hep G2,HeLa,QBC939 and K562 were used for the in vitro anticancer studies. The anticancer effects were detected by cell counting or MTT assay. Results The inhibitory ratios of D6B2（25 μM,50 μM, 100 μM, 150 μM, 200 μM） were 24.94%, 42.11%, 65.74%, 70.22%, 73.11% on CNE;23.15%,54.56%,62.95%,70.14%,75.18% on Hep G2; 31.34%,60.76%,78.43%,85.78%,90.75% on HeLa; 5.97%,12.05%,28.44%, 35.28%, 51.31% on QBC939; 18.20%, 35.48%, 46.76%, 58.44%,57.32% on K562. The IC50 value against CNE,Hep G2,HeLa,QBC939 and K562 were 66.9 μM, 60.98 μM,40.7 μM,197.07 μM and 120.06 μM,respectively. The inhibitory ratios of D6B2（25 μM, 50 μM, 100 μM,150μM, 200μM） on HeLa were 7.96%,9.56%,10.98%,14.00%, 17.33% at 24 h;10.62%,25.96%,47.63%, 48.24%, 49.03% at 48 h;18.08%,53.68%, 85.55%, 87.86%, 82.07% at 72 h. The CDI value of D6B2 at 25 μM, 50 μM and 100 μM was 0.039,0.019 and 0.014, respectively, when used with 10 μM DDP.Conclusion D6B2 showed significant in vitro anticancer effects on human cancer cells. Its in vitro anticancer activity was dose-dependent and time-dependent. D6B2 and DDP had synergistic in vitro anticancer effects.

关 键 词：4-乙氧基-2-羟基-6-甲基苯甲酸 抗肿瘤作用 联合抗肿瘤作用 顺铂 人鼻咽癌细胞 人肝癌细胞 人子宫颈癌细胞 人胆管癌细胞 人白血病细胞 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学]