摘要
目的研究鬼臼毒素纳米脂质体(POD-nlip)对人白血病多药耐药细胞株K562/ADM细胞的凋亡诱导和耐药逆转效应。方法薄膜超声分散法制备POD-nlip。分别以不同浓度的鬼臼毒素(POD)和POD-nlip处理K562/ADM细胞,MTT法检测细胞的增殖活性,光学显微镜观察细胞形态学变化,Annexin V/PI染色检测细胞凋亡。结果K562/ADM细胞对POD耐受约6～30倍。对K562/ADM细胞的抑制作用,POD-nlip 24、48和72h的半数抑制浓度(IC_(50))分别为5.37、1.59和0.40μg/mL,而POD为9.06、2.82和1.67μg/mL,POD-nlip明显高于POD;0.1μg/mL POD-nlip处理24和72 h,Annexin V/PI染色检测K562/ADM细胞凋亡率分别为95.6%和95.7%,但72 h时以晚期凋亡为主;形态上细胞出现胞膜起泡、核染色质浓集、聚集在核膜下呈半月形或指环状、核固缩或核碎裂、凋亡小体等典型的凋亡形态学改变。K562/ADM细胞对POD的耐受性得到部分逆转,敏感性提高约2～4倍。结论POD制备成纳米脂质体可增强K562/ADM细胞的增殖抑制和凋亡诱导效应,部分逆转其耐药性。
Objective To study the reversion of drug-resistance and induction of apoptosis by podophyllotoxin nanoliposome （POD-nlip） in human multidrug-resistafit human leukemia cell line K562/ADM cells. Methods POD-nlip was prepared using a dried film-ultrasonic procedure. K562/ADM cells were treated with different concentrations of podophyllotoxin （POD） and POD- nlip in vitro, the cell proliferating activity was assessed by MTT assay, cell morphology and Annexin V/PI staining were employed to determine apoptosis in K562/ADM cells. Results K562/ADM cells were resistant to POD by about 6 to 30 times. The inhibitory effect of POD- nlip on K562 cells was much higher than that of POD, the 50% inhibitory concentration （IC50） at 24, 48 and 72 h was 5.37, 1.59 and 0.40 μg/mL, respectively, and 9.06, 2.82 and 1.67 μg/mL for POD. After administered with 0.1 μg/mL POD-nlip for 24 and 72 h, the apoptotic rates of K562/ADM cells detected by Annexin V/PI staining were 95.6% and 95.7%, respectively. At 72 h, the cells mainly showed late apoptotic phenomena, and the cells showed typical apoptotic morphological changes in both POD-nlip and POD-treated cells. The tolerance of K562/ADM cells to POD was reversed in part, and the sensitivity of K562/ADM cells to POD was increased by approximately 2 to 4 folds. Conclusion POD-nlip remarkably inhibits the proliferation of K562/ADM cells and induces their apoptosis, and partially reverses the resistance of the cells to POD.
出处
《兰州大学学报（医学版）》
CAS
2008年第1期1-4,9,共5页
Journal of Lanzhou University（Medical Sciences）
