AIM To investigate the local effect of phosphorus-32 glass microspheres (32 P-GMS) on hepatocellularcancer and its relation with chemoembolism.MVIETHODS (① Thirty-two BALB/c nu/nu nude mice were divided randomly into four groups, control groupand 3 treatment groups. Every mouse was implanted with human liver cancer cell line subset (H-CS). 32p-GMS amalgamated in iodine oil was injected directly into the tumor mass. After 2 wk, all animals but thosein the control group, were injected with 32p-GMS in the dosage of 880cGY, 1760cGY and 3520cGY formouce groups Ⅰ, Ⅱ and Ⅲ respectively. The histological reactions of tumor mass were observed; multidrugresistance (MDR) expressed p-glycoprotein was detected by flow cytometry. ②Forty-three patients withhepatocellular carcinoma based on the evidence from B sonography or CT and serum AFP >400 ng/mL orcytological and histological evidences in some cases with the negative AFP were divided randomly into twogroups, group Ⅰ treated with 32p-GMS (absorbed dose of 50Gy- 100Gy) alone, group Ⅱ treated with 32p-GMS and chemotherapeutics (half-dosage, doxorubicin 20mg/m2, cisplatin 30mg/m2). 32 P-GMS wasinjected through intra hepatic artery in these cases with single massive type and multi-nodular type. Everypatient was repeatedly treated with this method for 2 - 3 times. For evaluating the therapeutic results. Themodified WHO criteria for tumor therapy standard is the.RESULTS (①) Animal bearing tumors showed that the mass decreased markedly and the inhibitive ratesattained 66.53%, 83.06% and 91.53% in the absorbed doses ranged form 880GY, 1760Gy and 3520Gyrespectively (P<0.05, ANOVA). Flow cytometry detected MDR expressed p-glycoprotein decreased from68.2 ± 4.6 in control to 43.6 ± 3.4, 35.3 ± 4.3 and 33.2 ± 3.8 (P<0.05, compared with control, t-test) inthe cells from the tumors. (②) The foci in group Ⅰ revealed decreased in size dramatically with effective rate of71.43%, compared with 86.36% in the group Ⅱ (P<0.05, Chi-squaur test). The median survival period ofthe patients were 532 and 564 d in group Ⅰ and Ⅱ respectivcey (Kaplan-Meire method).CONCLUSION The enhanced effectiveness of the local treatment of 32 P-GMS conjugated withchemotherapeutics may be related to the local action on the MDR expressed p-glycoprotein.

MK-801对耐苯妥英钠和卡马西平癫(癎)大鼠模型脑表达P-糖蛋白的影响

癫(癎)是神经科仅次于脑血管意外的常见疾病,其中大约有30%的患者对多种抗癫(癎)药物表现耐药,癫(癎)发作得不到有效控制,被称之为难治性癫(癎).难治性癫(癎)患者对药物产生耐药的机制还不明确.研究表明癫(癎)病灶内高度表达P-糖蛋白(P-glycoprotein,PGP)[1],PGP是一种多药转运蛋白,能够分解ATP获能从而逆浓度梯度将抗癫(癎)药物转运出脑组织,减少了癫(癎)病灶内的药物浓度,降低了药物的疗效,上述机制可能参与了难治性癫(癎)患者对多种抗癫(癎)药物产生耐药.

Objective To investigate the anti-tumor effect of ZM-66 on multidrug-resistant leukemic cell line K562/ADM.
Methods The K562/ADM cells were treated with varying concentrations (0, 1, 2, 4×10-3 mmol/L) of ZM-66 or etoposide for 24 hours. The proliferation was detected by Sulforhodamine B Sodium Salt (SRB) assay and apoptosis was detected by flow cytometry analysis and fluorescent staining. In addition, the expression levels of p53 and bax genes in K562/ADM cells were detected by RT-PCR analysis. The level of P-glycoprotein (P-gp), P53 and Bax protein in K562/ADM cells were detected by Western blot assay.
Results SRB assay demonstrated that etoposide had little inhibitory effect on K562/ADM cells, whereas ZM-66 (1, 2, 4×10-3 mmol/L) had significantly inhibitory effect on K562/ADM cells (all P<0.01). The acridine orange/propidium iodide dual staining showed that there were typical condensation of chromatin and nuclear fragmentation nuclei with red color in ZM-66 treated cells. Flow cytometric analysis showed that there was a significantly increase of apoptotic cells in K562/ADM cells after treated with ZM-66. RT-PCR showed that the p53 and bax mRNA expression levels in K562/ADM cells treated with ZM-66 at 1, 2, 4×10-3 mmol/L were higher than those in the cell without treatment. Western blot showed that the P53 and Bax protein expression levels in K562/ADM cells treated with ZM-66 at 2, 4×10-3 mmol/L were higher than those in the cell without treatment. But the P-gp protein expression level in K562/ADM cells treated with ZM-66 at 2, 4×10-3 mmol/L was gradually lower than those in the cell without treatment.
Conclusion ZM-66 is able to induce cell death by apoptosis in vitro, as a result of the reverse of the apoptosis resistance in drug-resistant K562/ADM cells by modulating expression of key factors associated with apoptosis induction.

PI3K特异性抑制剂LY294002对卵巢癌紫杉醇耐药细胞株逆转作用的研究

目的:研究磷脂酰肌醇-3-激酶(PI3K)特异性抑制剂LY294002对卵巢癌紫杉醇耐药细胞株(A2780/Taxol)多药耐药逆转的影响.方法:将PI3K特异性抑制剂LY294002处理卵巢癌紫杉醇耐药细胞24 h后,用CCK-8(Cell Counting Kit-8)法检测细胞的增殖速度、对紫杉醇敏感性的分析;采用流式细胞技术检测细胞周期和凋亡.应用Western blot检测细胞中P-glycoprotein(P-gp)、Akt和p-Akt蛋白的表达情况.结果:用LY294002处理A2780/Taxol细胞后细胞增殖速度变慢、对紫杉醇的半数抑制浓度(IC50)降低.实验组和对照组细胞的凋亡率分别是(2.64±0.90)%和(10.98±1.16)%(P<0.05).LY294002处理后的G0/G1期细胞增加,S期明显减少,差异有统计学意义(P<0.05).LY294002处理后的细胞与对照组相比P-gp和p-Akt的蛋白表达降低.结论:LY294002能够有效的逆转卵巢癌紫杉醇耐药细胞A2780/Taxol产生的多药耐药.

P-glycoprotein的新功能在肿瘤研究中的进展

肿瘤多药耐药性（multiple drug resistance，MDR）的发生往往伴随着多药耐药基因如MDR1、MRP1和BCRP等高表达，其中MDR1基因编码的P-糖蛋白（P-glycoprotein，P-gp）是目前公认可以诱发癌细胞发生MDR的重要分子。传统研究认为P-gp主要是作为一个药物泵将化疗药物从细胞内排出从而导致MDR。然而系列研究发现，除了介导MDR以外，P-gp还能够调节癌细胞的生长、增殖、凋亡、迁移和侵袭等其他生物学行为；而且研究表明P-gp的这些作用可以依赖，也可以不依赖于其药物泵的功能。这些结果表明P-gp能够通过一些新的机制促进肿瘤的进展。本文主要针对P-gp在促进肿瘤进展中的作用进行综述。

局灶性脑缺血大鼠脑内mdr1/P-glycoprotein表达的变化

目的观察大鼠局灶性脑缺血损害后脑内mdr1/P-glycoprotein的表达变化.方法大鼠大脑中动脉栓塞法(MCAO法)制作局灶性脑缺血模型,脑切片免疫组织化学染色检测mdr-1/P-glycoprotein在脑内的表达部位及表达时程的变化.结果mdr-1/P-glycoprootein在缺血侧皮层和纹状体的血管内皮细胞表达增多,并出现在同侧损伤部位的神经元,其在损伤后2h开始出现,6h达到高峰,之后开始下降,到24h不能被检测到.结论大脑中动脉阻塞后可以诱导缺血损伤侧的血管内皮细胞P-glycoprotein过量表达,而同侧的神经元短暂表达P-glycoprotein.