| dc.description.abstract | Combined chemotherapy has drawn much attention for overcoming drug resistance and improving outcomes during the treatment of advanced stages of cancer. In the present study, cisplatin, oxaliplatin, LH5, gemcitabine, camptothecin and cucurbitacin B have been combined in a binary mode using three different sequences; i.e. bolus, 0/4 h and 4/0 h, in the ovarian and colorectal cancer models. Among the tested combinations of drugs, the combination of cisplatin with camptothecin and gemcitabine at all concentrations and for all sequences of addition, proved to be beneficial in overcoming cisplatin resistance in the A2780cisR ovarian cell line. In contrast, cisplatin, in combination with camptothecin; LH5, in combination with camptothecin; and gemcitabine, in combination with oxaliplatin, demonstrated a dose- and sequence-dependent enhancement in cell kill in the colorectal cancer models (HT-29 and/or Lim-1215 cell lines). The proteomic study revealed 20 proteins that showed significant changes in expression following different drug treatments in ovarian cancer models; e.g., cofilin 1, actin cytoplasmic 1, tropomyosin alpha-4 chain, tubulin beta chain, vimentin, peroxiredoxin-1, pyruvate kinase, peptidyl-prolyl cis-trans isomerase A, ATPase mitochondrial inhibitor, ATP synthase subunit beta, 60kDa heat shock protein, stress-70 protein, nucleophosmin, HSP 90-beta heat shock protein, GTP-binding nuclear protein Ran, elongation factor 1-alpha, histone H4, heterogeneous nuclear ribonucleoproteins C1/C2, annexin A1 and calmodulin-1. Among these proteins, peptidyl-prolyl cis-trans isomerase A, pyruvate kinase, nucleophosmin, elongation factor -1 alpha, histone H4 and calmodulin-1, have been identified as being anti-apoptotic proteins, whereas the ATPase mitochondrial inhibitor protein has been identified as being an apoptotic protein. Finally, bioinformatics analysis revealed that ovarian cancer patients with altered expressions of ACTB, HST1H4F, HNRNPC, HSP90AB1 and PKM genes, had lower survival rates, in comparison with the control group. | en_AU |
