摘要
目的:探讨三氧化二砷(As2O3)体外逆转人肝癌细胞多药耐药性的作用及机制.方法:MTT法检测As2O3的细胞毒作用和处理前后耐药细胞对化疗药物的敏感性,用流式细胞仪检测细胞内阿霉素浓度,通过RT-RCR检测MDR1基因的表达.结果:As2O3在0.25 mg/L剂量以下时对HepG2和HepG2/ADM耐药细胞株的抑制率均小于15%,半数抑制率(IC50)分别为1.02和1.34 mg/L,无细胞毒剂量0.2 mg/L的As2O3能部分逆转HepG2/ADM细胞对阿霉素、顺铂(CDDP)、丝裂霉素(MMC)、5-氟尿嘧啶(5-FU)的耐药性,逆转倍数分别为2.92,3.09,2.13,2.60倍.同时无细胞毒剂量0.2 mg/L的As2O3能使HepG2/ADM细胞内阿霉素浓度明显增加,MDR1表达下降.结论:As2O3具有体外逆转人肝癌细胞多药耐药性的作用,可能与下调MDR1表达、增加细胞内药物积累有关.
AIM: To explore the reversing effect of arsenic trioxide (As203) on the multidrug resistance (MDR) of human hepatocellular carcinoma HepG2/ADM cells in vitro and its potential mechanism.
METHODS: MTT assay was used to test the toxicity of As2O3 and the chemosensitivity to chemotherapeutics in As2O3-treated HepG2 and HepG2/ADM cells. Flow cytometry was used to determine the concentration of intracellular adriamycin (ADM). The expression of MDR1 was measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The inhibitory rates of HepG2 and HepG2/ADM cells caused by AS2O3 were lower than 15% under the dose of 0.25 mg/L, and the IC50 were 1.02 and 1.34 mg/L, respectively. As203 at 0.2 mg/L partly overcame the MDR of HepG2/ADM cells. The reverse efficiencies (multiples) to ADM, cisplatin (CDDP), mytomy- cin (MMC), 5-fluororacil (5-FU) were 2.92, 3.09, 2.13 and 2.60, respectively. Furthermore, after exposure to 0.2 mg/L AS203, the concentration of ADM was significantly increased while MDR1 expression was partially decreased in HepG2/ ADM cells.
CONCLUSION: AS2O3 can reverse the multidrug resistance of human hepatocellular carcinoma cells in vitro, and the possible mechanism is related to the down-regulated expression of MDR1 and raised concentration of drug inside the cells.
出处
《世界华人消化杂志》
CAS
北大核心
2006年第27期2691-2694,共4页
World Chinese Journal of Digestology
关键词
肝癌
多药耐药
三氧化二砷
Hepatocellular carcinoma
Multidrug resistance
Arsenic trioxide