[Synergistic cytotoxic effect of immunotoxin HEL-PE38KDEL and cis-platin against tumor cells].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Wang
Jin-song
JS
Department of General Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, P. R. China.
Wang
Shen-ming
SM
Chen
Guo-rui
GR
Yang
Da-jun
DJ
D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D014176:Protein Biosynthesis; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D017304:Annexin A5; D000970:Antineoplastic Agents; D000922:Immunotoxins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002945:Cisplatin