Abstract
Abstract We have previously reported that intercellular adhesion molecule-3 (ICAM-3) is associated with various cancer cell physiologic responses including developing cellular radio-resistance. In this report, we studied whether ICAM-3 exerts an additional effect on development of resistance against anti-cancer drug because drug/radiation resistance of cancer usually displays cross-resistance. We treated several anti-cancer drugs including, paclitaxel (Ptxl), 5-fourouracil (5-FU), and etoposide (Eto), to an ICAM-3 over-expressing stable transfectant or empty vector- transfected control NCI-H1299 non-small cell lung cancer (NSCLC) cell line (p53 and PTEN null cell). Ratios of cell survival against each drug were detected with microculture tetrazolium (MTT) assay. ICAM-3 stable transfectants showed less cell death compared with empty vector-transfected cells by Ptxl treatment. The ICAM-3 stable transfectants also showed a resistance against cell death induced by vincristine (VCS), another microtubule-damaging reagent. In clonogenic assay and cell counting assay, we also observed significant drug-resistance against microtubule-damaging reagents in ICAM-3 stable transfectant cell line. Ptxl/VCS-treated control control transfectant cells showed more apoptotic cell death and activation of caspase-3/-8 than those of ICAM-3 stable transfectant cell line at 96 hour after drugs treatments. Blockage of p44/42 MAPkinase and PI3-kinase/Akt pathway by treatment of pharmaceutical inhibitors increased Ptxl/VCS-induced apoptotic cell death. However, in same condition, ICAM-3 stable transfectant cell line showed relatively less cell death. We also detected ICAM-3 inhibited Ptxl/VCS-induced degradation of mitochondrial anti-apoptotic molecules including Bcl-2, Bcl-XL, and Mcl-1 in dose-dependent manner. These results indicate that ICAM-3 endowed drug-resistance of cancer cells against microtubule-damaging reagent via modulation of apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 700. doi:10.1158/1538-7445.AM2011-700
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