Dataset Information

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

ABSTRACT:

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 docetaxel 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.

SUBMITTER: Donix L

PROVIDER: S-EPMC9114061 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Donix Lukas L Erb Holger H H HHH Peitzsch Claudia C Dubrovska Anna A Pfeifer Manuel M Thomas Christian C Fuessel Susanne S Erdmann Kati K

Journal of cancer research and clinical oncology 20220112 6

<h4>Purpose</h4>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 docetaxel chemotherapy-two commonly applied treatment modalities in prostate cancer-influences the cisplatin (CDDP) tolerance in mCRP ...[more]

PMID: 35020044

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Project description: Ovarian cancer (OC) is the most lethal of the gynecologic cancers, and platinum-based treatment is a part of the standard first-line chemotherapy regimen. However, rapid development of acquired cisplatin resistance remains the main cause of treatment failure, and the underlying mechanism of resistance in OC treatment remains poorly understood. Faced with this problem, our aim in this study was to generate cisplatin-resistant (CisR) OC cell models in vitro and investigate the role of epithelial-mesenchymal transition (EMT) transcription factor Twist on acquired cisplatin resistance in OC cell models. To achieve this aim, OC cell lines OV-90 and SKOV-3 were exposed to cisplatin using pulse dosing and stepwise dose escalation methods for a duration of eight months, and a total of four CisR sublines were generated, two for each cell line. The acquired cisplatin resistance was confirmed by determination of 50% inhibitory concentration (IC50) and clonogenic survival assay. Furthermore, the CisR cells were studied to assess their respective characteristics of metastasis, EMT phenotype, DNA repair and endoplasmic reticulum stress-mediated cell death. We found the IC50 of CisR cells to cisplatin was 3-5 times higher than parental cells. The expression of Twist and metastatic ability of CisR cells were significantly greater than those of sensitive cells. The CisR cells displayed an EMT phenotype with decreased epithelial cell marker E-cadherin and increased mesenchymal proteins N-cadherin and vimentin. We observed that CisR cells showed significantly higher expression of DNA repair proteins, X-ray repair cross-complementing protein 1 (XRCC1) and poly (ADP-ribose) polymerases 1 (PARP1), with significantly reduced endoplasmic reticulum (ER) stress-mediated cell death. Moreover, Twist knockdown reduced metastatic ability of CisR cells by suppressing EMT, DNA repair and inducing ER stress-induced cell death. In conclusion, we highlighted the utilization of an acquired cisplatin resistance model to identify the potential role of Twist as a therapeutic target to reverse acquired cisplatin resistance in OC.

Dataset Information

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

Purpose

Methods

Results

Conclusion

Publications

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

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