Cui Jing, Ding Jing, Wu Yi-Ping, Liu Fu-Qiang, Liu Xiao-Chao, Wang Yang
Department of Hematology, Beijing Tongren Hospital, Capital University of Medical Sciences, Beijing100730, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Aug;15(4):756-61.
This study was purposed to investigate the reversal effect of sodium selenite on multidrug resistance in adriamycin-resistant leukemic cell line K562/ADR and its mechanisms. The cytotoxicity and the reversal effect of sodium selenite on K562/ADR cells were assayed by MTT method; the apoptosis rate of K562 and K562/ADR cells were detected by flow cytometery, the mRNA expressions of mdr1 and bcl-2 were measured by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The results showed that 10 micromol/L sodium selenite significantly increased the cytotoxicity of adriamycin to K562/ADR cell and the reverse index (RI) was 2.31; the early apoptosis rate of K562 cells was elevated after treatment with 5 micromol/L Na(2)SeO(3) for 48 hours; and the medium-term and late apoptosis rate was elevated after treatment with both 5 and 10 micromol/L Na(2)SeO(3) for 48 and 72 hours. Both doses of 5 and 10 micromol/L Na(2)SeO(3) increased the early apoptosis rate of K562/ADR at 48 hours, and also increased the medium-term and late apoptosis rate after treating for 48 and 72 hours. The apoptosis rate was higher at dose of 10 micromol/L than that at 5 micromol/L, the apoptosis rate at 72 hours also was higher than that at 48 hours. The expressions of mdr1 mRNA and bcl-2 mRNA were decreased significantly by 10 micromol/L sodium selenite. It is concluded that sodium selenite can reverse the multidrug resistance in K562/ADR partially by down-regulating the expressions of mdr1 mRNA and bcl-2 mRNA, and increasing apoptosis rate of K562/ADR cells.
本研究旨在探讨亚硒酸钠对阿霉素耐药白血病细胞株K562/ADR多药耐药的逆转作用及其机制。采用MTT法检测亚硒酸钠对K562/ADR细胞的细胞毒性及逆转作用；采用流式细胞术检测K562和K562/ADR细胞的凋亡率，采用半定量逆转录聚合酶链反应（RT-PCR）检测mdr1和bcl-2的mRNA表达。结果显示，10 μmol/L亚硒酸钠显著增加阿霉素对K562/ADR细胞的细胞毒性，逆转指数（RI）为2.31；5 μmol/L Na2SeO3处理48小时后K562细胞早期凋亡率升高；5和10 μmol/L Na2SeO3处理48和72小时后中期及晚期凋亡率升高。5和10 μmol/L Na2SeO3均使K562/ADR细胞48小时早期凋亡率增加，处理48和72小时后中期及晚期凋亡率也增加。10 μmol/L时凋亡率高于5 μmol/L，72小时凋亡率也高于48小时。10 μmol/L亚硒酸钠使mdr1 mRNA和bcl-2 mRNA表达显著降低。结论：亚硒酸钠可通过下调mdr1 mRNA和bcl-2 mRNA表达及增加K562/ADR细胞凋亡率部分逆转K562/ADR的多药耐药。
