Title DCA in combination with salinomycin exerts synergistic anti-cancer effect on colorectal cancer cell lines /
Authors Skeberdytė, Aistė ; Krasko, Jan Aleksander ; Antanavičūtė, Ieva ; Stankevičius, Vaidotas ; Sužiedėlis, Kęstutis ; Jarmalaitė, Sonata
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Is Part of COINS 2018 - 13th international conference of life sciences : 28 February-2 March 2018 Vilnius, Lithuania : [abstracts book] / Vilnius University Students Representation.. Vilnius : Vilnius University Students Representation. 2018, p. 153-154
Keywords [eng] Colorectal neoplasms ; Cell line, tumor ; Dichloroacetic acid ; Pyrans ; Antineoplastic combined chemotherapy protocols
Abstract [eng] In the present study we examined a hypothesis that salinomycin, an antibiotic ionophore, might efficiently potentiate the cytotoxic effect of dichloroacetate (DCA), a metabolic inhibitor, on cancer cells. We used two human colorectal cancer derived cell lines - DLD-1 and HCT116. First, we performed series of dose response experiments in 2D cell culture in mono- and combination therapy and evaluated effects, based on Chou-Talalay method. This analysis revealed that salinomycin in combination with DCA acted synergistically in both cell lines. Secondly, in order to recapitulate the in vivo tumour architecture, we tested doses, selected from 2D experiments, in 3D multicellular spheroid culture in mono- and in combination therapy. In such conditions, the effect of salinomycin and DCA was additive in DLD-1 and synergistic in HCT116 cell lines. Further, we demonstrate that synergistic effect of compounds might be related with inhibitory effect of DCA on multidrug resistance proteins (MRPs) and with reduction of intracellular pH that in cancer cells is elevated. The activity of MRPs as well as potency of certain drugs is pH-dependent. Finally in order to disclose the rationale for sensitivity variations to combination therapy between two cell lines, we have investigated gene expression profiling of DLD-1 and HCT116 cell lines in 2D and 3D cell cultures and presume that decreased sensitivity of DLD1 cells to combination therapy could be attributed to increased stemness of DLD-1 cells in 3D cultures compared to HCT116 cells.
Published Vilnius : Vilnius University Students Representation
Type Conference paper
Language English
Publication date 2018