Effects of gefitinib and small interfering RNAs targeting EGFRin the treatment of prostate eallcer

Abstract

Objective To probe into the inhibitory effects and mechanisms of Cefitinib and small interfering RNAs ( siRNA) targeting epidermal growth factor receptor ( EGFR) ( EGFR siRNA) against hormone independent prostate cancer (HIPC) in vitro and in vivo. Methods After PC-3 cells were trans-fected with lentivirus mediated EGFR siRNA recombinant or treated with Gefitinib (0-10 mg/L), MTT was used to measure cell growth inhibitory rate (IR), fluorescent real-time polymerase chain reaction (PCR) to detect EGFR mRNA level, and Western blotting to assay the expression of EGFR and its intracellular proteins, such as Akt, MAPK and PKC. Tumor growth was observed when EGFR siRNA or/and Gefitinib were used to treat mice with transplanted tumors. Results The IR of PC-3 cells was 40% -50% by using EGFR siRNA and transfection efficiency was 85%. Gefitnib inhibited the growth of PC-3 cells in a time-and concentration-dependent manner. The expression of EGFR mRNA and protein in PC-3 cells was down-regulated over 90% which was obviously higher than < 80% in Gefitinib group (P < 0.01) ; EGFR siRNA could significantly inhibit the expression of Akt and MAPK, but Gefitinib only significantly inhibit the expression of Akt. In the in vivo study, the tumor growth was inhibited significantly in Gefitinib group (53.95%) or Gefitinib + EGFR siRNA group (59. 28%) as compared with EGFR siRNA group (34. 83% ,P <0. 05). Conclusion EGFR pathways inhibitors could block PC cells growth effectively mainly via the down-regulation of the expression of EGFR and its intracellular protein Akt. Key words: Prostate carcinoma; Epidermal growth factor receptor; Small interfering ItNA