Evaluation of neurotoxicity of anticancer drugs using nematode Caenorhabditis elegans as a model organism

It is well established that platinum-based drugs, including oxaliplatin (L-OHP) and cis-platin (CDDP), as well as microtubule inhibitors paclitaxel (PTX) and vincristine (VCR), are associat-ed with chemotherapy-induced peripheral neuropathy (CIPN). In this study, we examined and compared the characteristics of neuropathies induced by L-OHP, CDDP, PTX, and VCR to evaluate whether Cae-norhabditis elegans (C. elegans) could serve as a model organism for human CIPN. Worms were cul-tured on nematode growth medium plates, and L1 larvae synchronized by gel filtration were employed. We then performed bioassays and examined motility. In the motility test, exposure was performed for 2, 24, and 48 hr, and time-dependent effects were measured for each exposure time and 24 hr after terminat-ing exposure. Herein, we observed that L-OHP and CDDP exerted concentration-dependent effects above a certain concentration, and PTX and VCR exerted concentration-dependent negative effects in the bio-assay. Motility recovered in L-OHP-, PTX-, and VCR-treated worms on terminating exposure. However, CDDP exposure tended to reduce motility even 24 hr after terminating exposure. L-OHP exposure could decrease motility 2 hr after exposure, with a trend toward recovery 24 hr after terminating drug exposure. The findings of the present study revealed that C. elegans could exhibit neuropathy characteristics sug-gested to be similar to those observed in humans, indicating that this organism could be a suitable model to explore human CIPN.