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

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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 study the dose-effect and time-effect relationship of 4-ethoxy-2-hydroxy-6-methylbenzoic acid (hereinafter referred to as D6B2) on the antitumor activity of multiple human tumor cells in vitro and to find out the sensitive tumor cell lines, To observe whether the compound and the clinical anti-cancer drugs have anti-tumor effect in vitro and the action form and intensity.Methods In vitro anti-tumor experiment was conducted to study the effect of different concentrations of D6B2 on human nasopharyngeal carcinoma cell line CNE, human hepatoma cell line Hep G2, Dose-response relationship of HeLa, human cholangiocarcinoma cell line QBC939 and human leukemia cell line K562 in vitro, and further to observe the time-effect relationship of the compound on HeLa cell inhibitory effect in vitro, The results showed that the inhibitory rates of D6B2 on CNE cells were 24.94%, 42.11%, 65.74%, 70.22%, 73.11% and IC50 of 66.9μM at the concentrations of 25μM, 50μM, 100μM, 150μM and 200μM, respectively The inhibitory rates of Hep G2 cells were 23.15%, 54.56%, 62.95%, 70.14%, 75.18% and IC50 of 60.98μM, respectively. The inhibitory rates of HeLa cells were 31.34%, 60.76%, 78.43% and 85.78% 90.75% , The IC50 was 40.7μM; the inhibitory rates of QBC939 cells were 5.97%, 12.05%, 28.44%, 35.28%, 51.31% and IC50 of 197.07μM, respectively. The inhibitory rates of K562 cells were 18.20%, 35.48%, 46.76% , 58.44%, 57.32% and IC50 of 120.06 μM respectively.The inhibition rates of D6B2 on HeLa cells for 24 h were 7.96%, 9.56%, 10.98%, 14.00% and 17.33%, respectively, and the inhibitory rates after 48 h were 10.62% and 25.96% The inhibitory rates of 47.63%, 48.24%, 49.03% and 72 h were 18.08%, 53.68%, 85.55%, 87.86% and 82.07%, respectively.D6B2 was administrated with 10μM DDP in the doses of 25μM, 50μM and 100μM, Value of 0.039, 0.019 and 0.014, respectively.Conclusion D6B2 has significant antitumor activity against CNE, Hep G2, HeLa, QBC939 and K562 cells in vitro, and there is a significant dose-response relationship between D6B2 and human cervical cancer cell line HeLa D6B2 has a time-effect relationship with HeLa in vitro.D6B2 has significant synergistic anti-tumor effect with cisplatin in clinical anti-cancer drug.
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