Effect of zoledronic acid exposure on Ki-67 expression and proliferation in MCF7 cells resistant to apoptosis induction.

• DOI: 10.1200/jco.2011.29.15_suppl.e21129
• Publication Date: 2017-02-23T18:58:03Z
• Authors: U. Haus; R. Ebert; J. Meissner-Weigl; S. Zeck; L. Klein-Hitpass; T. D. Rachner; P. Benad; A. Athari; L. Hofbauer; F. Jakob
• Keywords: Zoledronic Acid; Growth inhibition; Farnesyl pyrophosphate; Mevalonate pathway

e21129 Background: Bisphosphonates (BP) and the RANK-ligand antibody denosumab (D) are used for treatment of bone metastases. Low to high concentrations zoledronic acid (ZA) can induce tumor cell apoptosis in vitro via inhibition mevalonate pathway and/or accumulation ATP analog ApppI. Clinical studies indicate a benefit relapse survival with supportive ER-positive breast cancer using zoledronate (ZA), but molecular mechanisms involved under debate. Methods: MDA-MB-231 MCF-7 cells were treated 3 h (pulse treatment) 72 (permanent 5 – 100 µM ibandronate (IBN), alendronate (ALN), risedronate (RIS) ZA 1 ng/ml D comparison. Apoptosis proliferation was determined after h. Rescue experiments BP effects done geranylgeranyl-pyrophosphate (GGPP) atorvastatin (Ator). Microarray hybridizations performed identify target genes MCF-7. Results: Permanent pulse exposure induced inhibited without affecting apoptosis. While IBN, ALN RIS inferior induction MDA-MB-231, they equipotent GGPP rescued not antiproliferative MCF-7, while Ator latter. qPCR immunocytochemistry identified KLF2, KLF4, KLF6 Ki-67 as RANKL did affect untreated or pretreated terms Conclusions: In summary we show here direct other on expression relevant cells, which relatively resistant ZA-induced comparison MDA-MB-231. these effects, possibly indicating that rather due analogs than protein prenylation. had no basal conditions future should address context estrogens gestagens also coculture cells.