Our data reveal that IFN-α can exert its antitumor effect through a non-canonical JAK-STAT pathway in the bladder cancer cells with low activity of IFN pathway, and the TPL2 inhibition is another function of IFN-α in the context of bladder cancer therapy.
RT-qPCR and western blotting demonstrated that cytokines IL-2, IFN-α and IFN-γ markedly upregulated PD-L1 mRNA expression rates and protein levels in bladder cancer T24 cells (P<0.05), but had no significant effect in non-tumor SV-HUC-1 cells.
Here, we investigated whether a component of Ad-IFN-induced cell death involves protein overload-induced endoplasmic reticulum (ER) stress, using an IFNα-resistant human bladder cancer cell line (KU7), and the normal human urothelial cell line, TERT-NHUC, as preclinical models.
The results demonstrate that IFN acts synergistically with ATRA and 9cRA in the growth and apoptosis of bladder cancer cells in vitro and suggest that this combination has a potential for the treatment of transitional cell carcinoma of the bladder.
Surprisingly, in vitro, Ad-IFNalpha also caused caspase-dependent death of bladder cancer cell lines that were resistant to high concentrations of IFN-alpha protein, including the cell line used in vivo.
Mouse IFN inhibited the development of transformed foci in NIH 3T3 cultures transfected with the viral Ha-MuSV(ras) and Mo-MuSV(mos) oncogenes, or with the human bladder carcinoma ras EJ/T24 DNA.