Characterisation of Drug-Resistant Neuroblastoma Cell Lines

Resistance acquisition to chemotherapy is a major cause of treatment failure in high-risk neuroblastoma. This report focused on the use of drug-adapted neuroblastoma cell lines as pre-clinical models of acquired drug resistance. Results indicated intact cell MALDI-ToF mass spectrometry (MS) fingerprinting to be a promising technique for the authentication of drug-adapted cancer cell lines that cannot be discriminated from their parental cell lines by standard methods like short tandem repeat analysis, but further optimisation is required. MS fingerprinting and the determination of platinum drug-resistance profiles in 10 single cell-derived clonal sub-lines of the docetaxel-adapted UKF-NB-3 sub-line UKF-NB-3rDOCE10 revealed a noticeable heterogeneity. Further studies need to be performed in other cell line models and including additional anti-cancer agents to learn more about the heterogeneity in drug-resistant cancer cell populations in comparison to the respective parental cancer cell populations. Newly synthesised platinum- and palladium-based compounds displayed encouraging anti-cancer efficacy in the neuroblastoma cell line UKF-NB-3 and its sub-lines adapted to cisplatin (UKF-NB-3rCDDP1000), carboplatin (UKF-NB-3rCARBO2000), or oxaliplatin (UKF-NB-3rOXALI2000) warranting further studies in additional cell lines and animal experiments. 1H-NMR-based metabonomics characterisation of UKF-NB-3, UKF-NB-3rCDDP1000, UKF-NB-3rCARBO2000, and UKF-NB-3rOXALI2000 revealed remarkable differences and did, thus, not suggest that a certain sub-population of pre-existing cancer cells was selected during UKF-NB-3 cell adaptation to these closely related platinum drugs. Further research will have to show the variability of the resistance formation process when the same cell line is adapted to the same drug in parallel independent experiments. In conclusion, the data presented here provide initial information for the further use of drug-adapted cancer cell lines.