Sensitization to oxaliplatin in HCT116 and HT29 cell lines by metformin and ribavirin and differences in response to mitochondrial glutaminase inhibition

SILVINA M. RICHARD; VERÓNICA MARTINEZ MARIGNAC

JOURNAL OF CANCER RESEARCH AND THERAPEUTICS

MEDKNOW PUBLICATIONS

Lugar: New Dehli; Año: 2015

0973-1482

Aim of study: In the present study, we evaluated the effect of ribavirin and metformin on the sensitivity of oxaliplatin and5‑fluorouracil (5‑FU) on colon cancer.Materials and Methods: Cell viability of two commercially available colon cancer cell lines (HT29 and HCT116) were analyzed bysulforhodamine B (SRB) assay.Results: A clinically achievable and nontoxic concentration of ribavirin and metformin showed a significant synergistic effect onoxaliplatin in HT29 and HCT116 cell lines. Ribavirin showed a synergistic effect on oxaliplatin in HT29 (R = 2.93, P < 0.001) andHCT116 (R = 1.71, P < 0.001), while only in HT29 metformin synergized with oxaliplatin by 2.66 (± 0.28, P < 0.01). In addition,both cell lines showed significant differences in response to Compound 968, inhibitor of mitochondrial glutaminase activity.Conclusion: The data suggested that these cell lines not only turn to metabolic different sustainability process after oxaliplatintreatment but that they also have different basal metabolic requirements of glutamine in vitro which can be exploits in the future forcolorectal cancer (CRC) treatment and further studies are required.