Resistance and toxicity are the major barriers to successful
cancer chemotherapies. Developing molecules that reduce drug resistance and improve
antineoplastic effects is of great interest for
cancer research; ideally, these substances should not affect the pharmacodynamics of the chemotherapeutic agent while providing a synergistic
antineoplastic effect. In this study, we tested in vitro co-administration of the
antineoplastic agents cisplatin or
paclitaxel with
probenecid, an
anion channel inhibitor, in a panel of
cancer cell lines to determine the cytotoxicity and synergistic effects of these
drug combinations. In addition, we measured the clonogenicity and apoptotic index in these cells. We observed a synergistic interaction between
probenecid and the chemotherapeutic agents, and increasing doses of
probenecid resulted in a significant decrease in the effective doses of the chemotherapeutic agents. For the
antineoplastic agent and
probenecid combinations, we found increased cell death, reduced colony formation, and a higher number of apoptotic cells, compared with treatment of
cisplatin or
paclitaxel alone. Further research is necessary to elucidate the molecular mechanisms by which the synergistic effect occurs. If these synergistic effects can be reproduced in vivo, the co-administration of
probenecid with different chemotherapeutic agents may provide a valid treatment in patients with
chemotherapy resistance.