The effect of a recombinant immunotoxin containing ricin toxin on the expression of apoptotic genes BAX and BCL-2 in colorectal and breast cancer cell lines

 Cancer is mainly caused by defect in natural regulation of programmed cell death (PCD). On the other hand, it is proved that, the EGFR is overexpressed on the surface of many malignant cell. Therefore, immunotoxin against EGFR, which consisting an antibody or fragment of an antibody linked to the toxic moiety is one of the most reliable strategies for cancer treatment. Here we evaluate the effect of a novel immunotoxin molecule harboring ricin, as a toxic moiety on the mRNA level of two main apoptotic molecules on cancerous cell lines.

 The Effects of immunotoxin molecule and it’s components including ricin toxin and antibody fragment on the mRNA level of pro- apoptotic BAX and anti-apoptotic BCL-2 and EGF receptor genes on the breast MDA-MB-468 and colorectal HCT-116 cancer cell lines were assayed by qRT-PCR. We used glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as a reference gene.

 Treatment with immunotoxin significantly increased the expression of BAX gene and decreased the expression of EGFR and BCL-2 genes (P<0.05) and induced apoptosis. Also, ricin toxin caused a significant decrease in BCL-2 and no significant increase in BAX in cancer cells and decreased EGFR only in breast cancer cells. The scFv part had no significant changes on genes expression.

 The present findings showed that the recombinant Panitumumab-Ricin protein, may be an appropriate candidate for the treatment of EGFR overexpressed cancers by induction in apoptosis pathway.