Acquired resistance to irradiation or docetaxel is not associated with cross-resistance to cisplatin in prostate cancer cell lines

Purpose: Platinum chemotherapy can be considered to treat metastatic castration-resistant prostate cancer (mCRPC) with
features of neuroendocrine differentiation. However, platinum compounds are generally only applied after the failure of
multiple prior-line treatment options. This study investigated whether acquired resistance against ionizing radiation or doc-
etaxel chemotherapy—two commonly applied treatment modalities in prostate cancer—influences the cisplatin (CDDP)
tolerance in mCRPC cell line models.
Methods: Age-matched parental as well as radio- or docetaxel-resistant DU145 and PC-3 cell lines were treated with CDDP
and their sensitivity was assessed by measurements of growth rates, viability, apoptosis, metabolic activity and colony
formation ability.
Results: The data suggest that docetaxel resistance does not influence CDDP tolerance in all tested docetaxel-resistant cell
lines. Radio-resistance was associated with sensitization to CDDP in PC-3, but not in DU145 cells. In general, DU145 cells
tolerated higher CDDP concentrations than PC-3 cells regardless of acquired resistances. Furthermore, non-age-matched
treatment-naïve PC-3 cells exhibited significantly different CDDP tolerances.
Conclusion: Like patients, different mCRPC cell lines exhibit significant variability regarding CDDP tolerance. The presented
in vitro data suggest that previous radiation treatment may be associated with a moderate sensitization to CDDP in an isogenic
and age-matched setting. Therefore, previous radiotherapy or docetaxel chemotherapy might be no contraindication against
initiation of platinum chemotherapy in selected mCRPC patients.