Abstract 4590: Abciximab manifests striking anti-tumor effects in sensitive and chemoresistant ovarian cancer cells

Abstract

Abstract Introduction: We have recently reported myeloperoxidase (MPO) to be expressed in epithelial ovarian cancer (EOC) cells and tissues. This finding was surprising, as MPO is known to be expressed only in cells of myeloid origin. We have also found that targeting β2 integrin (CD11b/CD18), a known ligand for MPO, resulted in significant anti-tumor effects. The objective of this study was to determine if targeting CD11b with a clinically approved drug that cross-reacts with CD11b will have anti-tumor efficacy for the treatment of sensitive and chemoresistant ovarian cancer. Methods: Human EOC cell lines MDAH-2774, SKOV-3, and A2780 and their chemoresistant counterparts were utilized for this study. Cells were treated for 24 hrs with increasing doses of docetaxel (0.0075, 0.01, and 0.025 μM) or cisplatin (0.1, 0.5 and 1.0 μM) with our without abciximab (5 or 10 μg/ml), an existing clinically approved anticoagulant drug. Abciximab is a human-murine chimeric antibody Fab fragment against platelet integrin glycoprotein IIb/IIIa (GP IIb/IIIa). Cytotoxicity was determined by the TACS MTT Cell Proliferation Assay. Data was analyzed using SPSS and significant cytotoxic effects were determined by one-way analysis of variance within groups (sensitive, resistant to docetaxel or cisplatin) followed by Tukey’s post hoc tests, and independent t-tests for comparison between groups. For the synergistic effect of abciximab and chemotherapy, the automated calculation of combination index values was conducted by CompuSyn software. A combination index method provides qualitative information on the nature of compound interaction (antagonistic, additive or synergistic effect) and was used to analyze the results. Statistical significance of p<0.05 was considered significant for all analyses. Results: Abciximab had significant cytotoxic effects in sensitive (40.8 ± 10.3 and 56.7 ± 5.3%), docetaxel resistant (30.0 ± 11.6 and 46.6 ± 10.0%), and cisplatin resistant (27.3 ± 7.9 and 41.9 ±7.0%) EOC cells at the 5 and 10 μg/ml dose, respectively, as compared to untreated controls (p<0.01). Abciximab is significantly more cytotoxic to sensitive as compared to cisplatin resistant cells (p<0.01), with no significant difference in killing as compared to docetaxel resistant cells (p=0.057). Treatment with chemotherapy combined with abciximab resulted in a synergist cytotoxic effect in all sensitive EOC cell lines, and in chemoresistant MDAH-2774 and SKOV-3 cell lines. For the cisplatin resistant A2780 cell line, synergist effects were only observed when combining abciximab with 1.0 μM cisplatin. Conclusions: The observed intriguing anti-tumor effects of abcixiamb in ovarian cancer cells indicates the potential for abciximab to be repurposed as a novel therapy for ovarian cancer. Citation Format: Ghassan M. Saed, Nicole M. Fletcher, Ira Memaj. Abciximab manifests striking anti-tumor effects in sensitive and chemoresistant ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4590. doi:10.1158/1538-7445.AM2017-4590