IL-8 inhibits bortezomib-induced apoptosis in ovarian cancer cells (1010.2)

Proteasome inhibition is a promising therapeutic strategy in a number of human cancers, including ovarian cancer, one of the most lethal human cancers. Bortezomib (BZ) is the first FDA approved proteasome inhibitor that has a remarkable anti-tumor activity in many hematological malignancies. In solid tumors, BZ has been less effective; however, the underlying mechanisms are not fully understood. The rationale behind BZ development and use was its inhibition of NFκB activity and resulting suppression of NFκB-dependent pro-inflammatory and anti-apoptotic genes. However, recent studies from our laboratory demonstrated that while BZ decreases expressions of most NFκB-regulated genes, it actually increases expression of the pro-inflammatory and pro-angiogenic chemokine, IL-8, in ovarian cancer cells. The goal of this study was to investigate whether the BZ-increased IL-8 expression regulates survival of ovarian cancer cells. Here, we show that suppression of IL-8 levels by siRNA significantly induces apoptosis...