刺囊酸及其衍生物的体外化疗增敏作用及机制研究

目的探讨刺囊酸及其衍生物的体外化疗增敏作用及其机制。方法体外培养人乳腺癌细胞MCF-7和人肝癌细胞HepG-2的敏感株和阿霉素耐药株，依次在阿霉素和受试化合物的作用下，以MTT法测定其IC₅₀，计算耐药倍数; 随后，对耐药株加入不同浓度组合的阿霉素和受试化合物进行共培养，以MTT法测定各组细胞活力，计算刺囊酸及其衍生物的MDR逆转倍数。结果刺囊酸及其衍生物在低浓度下无明显细胞毒活性，但却能增强耐药细胞对化疗药阿霉素的敏感性，逆转倍数最高可达15倍以上，并且几种刺囊酸衍生物的作用具有剂量依赖性; ELISA试验结果显示，刺囊酸及其衍生物抑制耐药株的P-gp表达，减少化疗药物从细胞中泵出，起到增敏作用。结论刺囊酸及其衍生物具有化疗增敏作用，其机制来源于对P-gp的抑制。

Study on Sensitization and Mechanism of EA and Its Derivatives in Vitro Chemotherapy

The paper is to investigate the derivatives of echinocystic acid(EA) and their application as chemosensitizer in vitro and their mechanism. The sensitive and adriamycin resistant strains of human breast cancer cell line MCF-7 and human hepatocellular carcinoma cell line HepG-2 were cultured in vitro and the IC₅₀ of adriamycin and its test compounds were determined by MTT method and then the resistance times were calculated. Subsequently, resistant strains were co-cultured with different concentration of adriamycin and its test compounds, MTT assay was used to determine the cell viability of each group, the test compounds to calculate the reversal times of EA and its derivatives.The results show that EA and its derivatives had less cytotoxicity at low concentration, but they could significantly enhance the sensitivity of drug-resistant cells to the chemotherapeutic drug adriamycin, and the reversal times could reach more than 15 times; EA derivatives are dose-dependent; EA and its derivatives inhibit the delivery of P-gp in resistant strains, and reduce the pumping of chemotherapeutic drugs from the cells, thus enhancing the sensitivity of the chemotherapeutic drugs.In conclusion, EA and its derivatives have chemosensitization effect, and the mechanism is partly or wholly attribute to the inhibition of P-gp.