IL-35 promotes pancreas cancer growth through enhancement of proliferation and inhibition of apoptosis: evidence for a role as an autocrine growth factor.

Interleukin-35 (IL-35), an IL-12 cytokine family member, mediates the immune inhibitory function of regulatory T cells (Treg). We assayed the presence of IL-35 in paraffin-embedded human pancreas cancer (PCAN) and unexpectedly found IL-35 was expressed mainly by epithelial derived PCAN cells, but not by Treg. We further examined the expression and effect of exogenous IL-35 in human PCAN cell lines and found IL-35 promoted growth and inhibited apoptosis in PCAN cell lines. IL-35 induced proliferation correlated with an increase in cyclin B, cyclin D, cdk2, and cdk4 and a decrease in p27 expression, while inhibition of apoptosis was associated with an increase in Bcl-2 and a decrease in TRAILR1. We conclude IL-35 is produced by PCAN in vivo and promotes PCAN cell line growth in vitro. These results might indicate an important new role for IL-35 as an autocrine growth factor in PCAN growth.

Hydrogen peroxide enhances radiation-induced apoptosis and inhibition of melanoma cell proliferation.

The efficacy of radiation therapy (RT) for melanoma is limited in part by its radioresistance. Here, we examined the radiosensitizing effect of hydrogen peroxide (H(2)O(2)) on a radioresistant melanoma cell line, HTB-65. We found that H(2)O(2) synergized with RT to inhibit melanoma cell proliferation and promote apoptosis. The antiproliferative effect of H(2)O(2)/RT correlated with increased expression of p15 and reduced expression of cyclin D, cyclin E, cyclin-dependent kinase (CDK)2 and CDK4. The pro-apoptotic effect of H(2)O(2) /RT correlated with reduced expression of the B-cell CLL/lymphoma (BCL)2. These data highlight the potential of H(2)O(2) as a radiation sensitizer for melanoma treatment and show that this warrants further study.