7 research outputs found
Genetic Diversity and Treatment Resistance in Prostate Cancer Cell Lines
Die Dissertationsarbeit untersucht genetische Varianten in Zellkulturmodellen des metastatischen und kastrationsresistenten Prostatakarzinoms. AuĂźerdem werden Mechanismen der Chemoresistenz, insbesondere der Resistenz gegen Cisplatin und Docetaxel in diesen Zelllinien untersucht.This Dissertation evaluates genetic variants found in cell culture models of metastatic castration resistant prostate cancer. Furthermore, mechanisms of resistance against the chemotherapeutic drugs cisplatin and docetaxel are investigated in these cell lines
Genetic Diversity and Treatment Resistance in Prostate Cancer Cell Lines
Die Dissertationsarbeit untersucht genetische Varianten in Zellkulturmodellen des metastatischen und kastrationsresistenten Prostatakarzinoms. AuĂźerdem werden Mechanismen der Chemoresistenz, insbesondere der Resistenz gegen Cisplatin und Docetaxel in diesen Zelllinien untersucht.This Dissertation evaluates genetic variants found in cell culture models of metastatic castration resistant prostate cancer. Furthermore, mechanisms of resistance against the chemotherapeutic drugs cisplatin and docetaxel are investigated in these cell lines
Genetic Diversity and Treatment Resistance in Prostate Cancer Cell Lines
Die Dissertationsarbeit untersucht genetische Varianten in Zellkulturmodellen des metastatischen und kastrationsresistenten Prostatakarzinoms. AuĂźerdem werden Mechanismen der Chemoresistenz, insbesondere der Resistenz gegen Cisplatin und Docetaxel in diesen Zelllinien untersucht.This Dissertation evaluates genetic variants found in cell culture models of metastatic castration resistant prostate cancer. Furthermore, mechanisms of resistance against the chemotherapeutic drugs cisplatin and docetaxel are investigated in these cell lines
PIAS1 is not suitable as a urothelial carcinoma biomarker protein and pharmacological target.
Urothelial cancer (UC) is one of the most common cancers in Europe and is also one of the costliest to treat. When first line therapies show initial success, around 50% of cancers relapse and proceed to metastasis. In this study we assessed the Protein inhibitor of activated signal transducers and activators of transcription (PIAS)1 as a potential therapeutic target in urothelial cancer. PIAS1 is a key regulator of STAT1 signalling and may be implicated in carcinogenesis. In contrast to other cancer types PIAS1 protein expression is not significantly different in malignant areas of UC specimens compared to non-malignant tissue. In addition, we found that down-regulation and overexpression of PIAS1 had no effect on the viability or colony forming ability of tested cell lines. Whilst other studies of PIAS1 suggest an important biological role in cancer, this study shows that PIAS1 has no influence on reducing the cytotoxic effects of Cisplatin or cell recovery after DNA damage induced by irradiation. Taken together, these in vitro data demonstrate that PIAS1 is not a promising therapeutic target in UC cancer as previously shown in different entities such as prostate cancer (PCa)
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 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-naĂŻve 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
Comprehensive Evaluation of Multiple Approaches Targeting ABCB1 to Resensitize Docetaxel-Resistant Prostate Cancer Cell Lines
Docetaxel (DTX) is a mainstay in the treatment of metastatic prostate cancer. Failure of DTX therapy is often associated with multidrug resistance caused by overexpression of efflux membrane transporters of the ABC family such as the glycoprotein ABCB1. This study investigated multiple approaches targeting ABCB1 to resensitize DTX-resistant (DTXR) prostate cancer cell lines. In DU145 DTXR and PC-3 DTXR cells as well as age-matched parental controls, the expression of selected ABC transporters was analyzed by quantitative PCR, Western blot, flow cytometry and immunofluorescence. ABCB1 effluxing activity was studied using the fluorescent ABCB1 substrate rhodamine 123. The influence of ABCB1 inhibitors (elacridar, tariquidar), ABCB1-specific siRNA and inhibition of post-translational glycosylation on DTX tolerance was assessed by cell viability and colony formation assays. In DTXR cells, only ABCB1 was highly upregulated, which was accompanied by a strong effluxing activity and additional post-translational glycosylation of ABCB1. Pharmacological inhibition and siRNA-mediated knockdown of ABCB1 completely resensitized DTXR cells to DTX. Inhibition of glycosylation with tunicamycin affected DTX resistance partially in DU145 DTXR cells, which was accompanied by a slight intracellular accumulation and decreased effluxing activity of ABCB1. In conclusion, DTX resistance can be reversed by various strategies with small molecule inhibitors representing the most promising and feasible approach