Wang Jin-song, Wang Shen-ming, Chen Guo-rui, Yang Da-jun
Department of General Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, P. R. China.
Ai Zheng. 2002 Apr;21(4):360-3.
The immunotoxin of HEL-PE38KDEL has been proven to be a novel biological reagent which has specific cytotoxic effect against breast cancer cells with positive erbB-2, 3, 4. However it has not been tested the interaction of the immunotoxin and the conventional chemical anti-cancer drugs. This study was designed to investigate the mechanism of the synergistic effect between HEL beta 1-PE38KDEL and cisplatin.
The tests of Annexin V binding and Western blot were performed to detect the apoptosis in the breast cancer cell lines MDA-MB-453, 2LMP, and the gastric cancer cell of N87 treated with single or drug combination.
In MDA-MB-453 and N87 with high expression of erbB-2, 3, 4, percentage of the apoptosis cell was significantly higher in the group treated with the drug combination than that in the group treated with the single drug (P < 0.01). To the contrast, in 2LMP cells with low expression of erbB-2, 3, 4, there was no difference between the drug combination and the single drug group (P > 0.05). In MDA-MB-453 and N87, degradation of PARP, caspase-3 was more in the group treated with the drug combination than that in the group treated with the drug alone. Overexpressions of bcl-2, mp53 were inhibited in the group treated by the drug combination. On the contrary overexpressions of bcl-2, mp53 were not inhibited in the group treated with the single drug. While these changes of PARP[poly (ADP)-ribose polymerase], caspase-3, mp53, bcl-2 could not be observed in the control cell line of 2LMP.
The combination of HEL beta 1-PE38KDEL and cis-platin could promote the synergistic effect on apoptosis in the target cancer cells with high expression of erbB-2, 3, 4 which might be one of the mechanism of these two drugs.
HEL-PE38KDEL免疫毒素已被证明是一种新型生物试剂，对erbB-2、3、4呈阳性的乳腺癌细胞具有特异性细胞毒性作用。然而，尚未对该免疫毒素与传统化学抗癌药物的相互作用进行检测。本研究旨在探讨HELβ1-PE38KDEL与顺铂协同作用的机制。
进行膜联蛋白V结合试验和蛋白质印迹法，以检测用单一药物或药物组合处理的乳腺癌细胞系MDA-MB-453、2LMP以及胃癌细胞N87中的细胞凋亡情况。
在erbB-2、3、4高表达的MDA-MB-453和N87中，药物组合处理组的凋亡细胞百分比显著高于单一药物处理组（P<0.01）。相比之下，在erbB-2、3、4低表达的2LMP细胞中，药物组合组与单一药物组之间无差异（P>0.05）。在MDA-MB-453和N87中，药物组合处理组的PARP、半胱天冬酶-3降解程度高于单一药物处理组。药物组合处理组中bcl-2、p53的过表达受到抑制。相反，单一药物处理组中bcl-2、p53的过表达未受到抑制。而在2LMP对照细胞系中未观察到PARP[聚（ADP-核糖）聚合酶]、半胱天冬酶-3、p53、bcl-2的这些变化。
HELβ1-PE38KDEL与顺铂联合使用可增强对erbB-2、3、4高表达的靶癌细胞凋亡的协同作用，这可能是这两种药物作用的机制之一。
