Inhibition of nuclear factor kappa B attenuates tumour progression in an animal model of renal cell carcinoma

Methods. The metastatic human RCC cell line, SN12K1, was inoculated into the left kidneys of severe combined immunodeficiency mice and the effect of semi-continuous PDTC treatment (50 mg/kg) on RCC growth analysed 5 weeks later. The analyses carried out in three groups (no treatment, RCC alone and RCC + PDTC) at 5 weeks were: renal weight, protein expression by immunohistochemistry and Western immunoblot, apoptosis (TdT-mediated nick end labelling and morphology) and mitosis (morphology). Results. PDTC significantly decreased RCC growth and the expression of NF-kappa B subunits (p50, p52, c-Rel and RelB), upstream IKK-beta and IKK-gamma, but did not induce any changes in the expression of I kappa B-alpha and I kappa B-beta. RCC growth was associated with a significant decrease in the expression of the anti-apoptotic proteins Bcl-2 and Bcl-(XL) and increase in pro-apoptotic Bax, all of which were reversed by PDTC. Cell proliferation was significantly reduced by PDTC. Conclusion. The results demonstrate the potential anti-cancer benefits of treating NF-kappa B positive RCCs with NF-kappa B inhibitors like PDTC.