siRNA is not more Effective than a First Generation Antisense Oligonucleotide when Directed against EGFR in the Treatment of PC-3 Prostate Cancer

Abstract

siRNA specifically directed against the epidermal growth factor receptor (EGFR) was compared to the previously described and effective MR2 oligo (also specific for EGFR) in a total of six comparative studies utilizing the chemotherapeutic agents Taxol, cisplatin and Cytoxan and the PC-3 prostate tumor line. When Taxol was administered in combination with either MR2 or siRNA, the MR2 was significantly more effective (p=0.000277) against PC-3 cells incubated for 24 h in their presence. In a sequential study in which a 24-h Taxol treatment was followed with either MR2 or siRNA for an additional 24 h, or in the reverse order where MR2 or siRNA was followed by Taxol, no significant differences were found. When cisplatin was similarly administered in combination with either MR2 or the siRNA, no significant differences in inhibition were found. In a subsequent study, in which a 24-h treatment with either MR2 or siRNA was followed by cisplatin for an additional 24 h, again no significant differences were found. Lastly, in a series of sequential administrations including Cytoxan the following was found. PC-3 cells treated for 24 h with Cytoxan followed by either MR2 or siRNA produced similar inhibition. When the cycle was reversed, with MR2 or siRNA treatment followed by Cytoxan, both treatments were again inhibitory, however the initial treatment with MR2 was significantly more effective (p=0.026095). We conclude that, although siRNA against EGFR has efficacy against the PC-3 line when administered either alone vs untreated controls, with Taxol vs Taxol alone, or with cisplatin vs cisplatin alone, it is not more effective than the better characterized MR2 oligo.