TY - JOUR T1 - The Hedgehog Pathway Inhibitor GDC-0449 Alters Intracellular Ca<sup>2+</sup> Homeostasis and Inhibits Cell Growth in Cisplatin-resistant Lung Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 89 LP - 94 VL - 32 IS - 1 AU - FEI TIAN AU - KATHRIN SCHRÖDL AU - ROSEMARIE KIEFL AU - RUDOLF MARIA HUBER AU - ALBRECHT BERGNER Y1 - 2012/01/01 UR - http://ar.iiarjournals.org/content/32/1/89.abstract N2 - Aim: Cisplatin resistance is an important issue in lung cancer. We aimed at investigating if the Hedgehog pathway inhibitor GDC-0449 is effective in cisplatin-resistant cells and if it alters intracellular Ca2+-homeostasis. Materials and Methods: The cytoplasmatic ([Ca2+]cyto) and endoplasmatic ([Ca2+])ER Ca2+ concentration of HCC (adeno carcinoma of the lung) and H1339 (small cell lung carcinoma) cells were measured with the calcium indicator dye Fura-2 AM. The expression of the inositol-1,4,5-trisphosphate receptor (IP3R) and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) were analyzed using western blot analysis. Results: GDC-0449 inhibited cell growth in cisplatin-naïve and -resistant cells. In both cell types, GDC-0449 increased [Ca2+]cyto and reduced endoplasmatic [Ca2+]ER. Cisplatin failed to considerably alter Ca2+ homeostasis in resistant cells. The effects of GDC-0449 on intracellular Ca2+ homeostasis were not mediated by an altered expression of IP3R or SERCA. Conclusion: GDC-0449 alters intracellular Ca2+ homeostasis and inhibits cell growth in cisplatin-resistant lung cancer cells. ER -