Abstract 1002 Regulation of Cisplatin Resistance in Lung Cancer Cells by Casein Kinase 2, CD44, and IGFBP-3

The basic operative mechanisms underlying cisplatin resistance in non-small cell lung cancer (NSCLC) remain poorly understood. Here, we show that blocking casein kinase 2 (CK2) activity increased sensitivity to cisplatin in the human non-small cell lung cancer cell lines, A549 and H1299. Phosphorylation of IGFBP-3 by CK2 (P-IGFBP-3) had no effect on its binding to IGF-1 but reduced its binding affinity to hyaluronan (HA). P-IGFBP-3 was less effective at decreasing cell viability or increasing apoptosis than IGFBP-3 in the absence or presence of cisplatin. IGFBP-3 was more effective at inhibiting HA-CD44 signaling than P-IGFBP-3 and augmented the effects of cisplatin. Cell sensitivity to cisplatin increased upon co-treatment with inhibitors targeted against PI3K, AKT, and NFκB while inhibiting p53 activity decreased A549 cell sensitivity to cisplatin. Our results shed light on a mechanism involving CK2, CD44, and IGFBP-3 in the regulation of cisplatin resistance in NSCLC cells.