Effect of curcumin and anti‐Ki‐67 siRNA on AY‐27 rat bladder cancer cells

Bladder cancer is the second most common malignancy of the urinary tract. The toxic side‐effects of the current treatments, including intravesical chemotherapy and immunotherapy are of major concern. Therefore, it is necessary to develop efficacious drugs that are less toxic. Curcumin, a well known dietary pigment has been shown to suppress pathways linked to ontogenesis. Another promising therapeutic approach is to silence abnormally up‐regulated genes in cancer using short interfering RNA (siRNA). Ki‐67 is a nucleolar phosphoprotein whose expression is significantly upregulated in bladder cancer. The objective of this study is to evaluate the combined effect of curcumin and anti‐Ki‐67 siRNA on rat bladder cancer cells (AY‐27). MTT assay was used to detect the cell viability; apoptosis and cell‐cycle analysis were determined by flow cytometry. Ki‐67 mRNA and protein expression were determined by RT‐PCR and immunoflourescence respectively. Data from our studies show that low concentrations of curcumin (10 μM) and anti‐Ki‐67 siRNA (10 nM), independently induce cell killing (20–30%) in bladder cancer cells. However, when treated together the effects were synergistic (55–60%), suggesting that the pathways leading to tumor cell apoptosis/necrosis are complementary. These findings suggest that the inhibition of Ki‐67 by siRNA combined with curcumin may be a reasonable approach in bladder cancer therapy