三氧化二砷、人参皂甙、β-榄香烯联合环磷酰胺对K562细胞株端粒-端粒酶系统的作用(英文)  

Effect of Ginseng Saponin, Arsenic Trioxide, β-elemene Combined with CTX on Telomere-Telomerase System in K562 Cell Line

作　　者：王一[1] 方美云[1] 

机构地区：[1]大连医科大学附属第一医院血液科,大连116011

出　　处：《中国实验血液学杂志》2006年第6期1089-1095,共7页Journal of Experimental Hematology

摘　　要：本研究探索三氧化二砷、人参皂甙、β榄香烯单独及联合环磷酰胺应用对K562细胞株端粒长度和端粒酶活性的调节作用,探讨上述药物抗白血病的作用机制。用不同浓度的三氧化二砷、人参皂甙及β榄香烯单独及联合环磷酰胺与人类红白血病细胞株K562共培养,采用PCR-ELISA法检测端粒酶活性、Southern杂交法检测端粒长度。观察上述药物对K562细胞端粒酶活性及端粒长度的影响。结果表明①经人参皂甙、三氧化二砷、β榄香烯及环磷酰胺作用后,K562细胞株端粒酶活性下降,下降程度呈浓度时间依赖性。当与环磷酰胺联合应用后,下降程度更明显。②三氧化二砷、人参皂甙、β-榄香烯作用后K562细胞的存活率下降,且抑制作用呈浓度、时间依赖性。当与环磷酰胺联合应用后,抑制作用更明显。③三氧化二砷、人参皂甙、β榄香烯及环磷酰胺作用于K562细胞株72小时后,端粒长度略有延长。结论三氧化二砷、人参皂甙、β榄香烯及环磷酰胺均能抑制K562细胞株的生长及端粒酶活性,抑制端粒酶活性可能是其抗肿瘤作用的机制之一;三氧化二砷、人参皂甙、β榄香烯与环磷酰胺联合应用后抑制作用增强;联合环磷酰胺可望降低上述药物的给药浓度。抑制端粒酶活性后,K562细胞株的端粒长度略有延长,提示除了端粒酶以外,白血病细胞可能存在其他的端粒长度调节机制。This study was aimed to investigate the modulating effects on telomere length and telomerase activity in K562 cells treated by arsenic trioxide, ginseng saponin, β-elemene alone or in combination with eyelophosphamide （CTX） and to explore the possible mechanism and new therapy for acute leukemia. Human erythroleukemie cell line K562 was co-cultured with the above-mentioned drugs. Cells were collected after 24, 48 and 72 hours for further detection. Telomere length and telomerase activity were detected by Southern-blot and PCR-ELISA respectively. The effects of these drugs were observed at different concentrations and exposure time. The results showed that （ 1 ） ginseng saponin, arsenic trioxide, β-elemene, or CTX could completely inhibit the telomerase activity of K562 cells at proper concentrations and exposure time. The inhibiting effects were enhanced when the three former drugs were used with CTX. Telomerase activity decreased proportionally with the concentrations and length of time. （2） viability of K562 cells was decreased after being co-cultured with arsenic trioxide, ginseng saponin, β-elemene and CTX. The level of inhibition depends on the concentration and exposure time. （3） telomere length of K562 cells was 5.36 ± 0.18 kb. After being co- cultured with those drugs for 72 hours, telomere length was 5.90 kb - 6.50 kb, significantly longer than that of control （ 5.18 -5.35 kb）. It is concluded that arsenic trioxide, ginseng saponin, and β-elemene can inhibit the growth and telomerase activity of K562 cells. The inhibiting effects were enhanced when they were used in combination with CTX. The depression of telomerase activity may be one of the mechanisms of anti-tumor effect. Less dosage and shorter course can be expected when arsenic trioxide, ginseng saponin, and β-elemene are used in combination with CTX. When telomerase activity was depressed, the telomere length prolonged a little, indicating K562 cell line may extend telomeres by some alternative way other than telomerase a

关 键 词：端粒-端粒酶 三氧化二砷 人参皂甙 Β榄香烯 K562细胞株 

分 类 号：R979.1[医药卫生—药品] R733.7[医药卫生—药学]