Cabazitaxel overcomes cisplatin resistance in germ cell tumour cells

TY - JOUR

T1 - Cabazitaxel overcomes cisplatin resistance in germ cell tumour cells

AU - Gerwing, Mirjam

AU - Jacobsen, Christine

AU - Dyshlovoy, Sergey

AU - Hauschild, Jessica

AU - Rohlfing, Tina

AU - Oing, Christoph

AU - Venz, Simone

AU - Oldenburg, Jan

AU - Oechsle, Karin

AU - Bokemeyer, Carsten

AU - von Amsberg, Gunhild

AU - Honecker, Friedemann

PY - 2016/9

Y1 - 2016/9

N2 - BACKGROUND: Cisplatin-based chemotherapy is highly effective in metastasized germ cell tumours (GCT). However, 10-30 % of patients develop resistance to cisplatin, requiring salvage therapy. We investigated the in vitro activity of paclitaxel and the novel taxane cabazitaxel in cisplatin-sensitive and -resistant GCT cell lines.METHODS: In vitro activity of paclitaxel and cabazitaxel was determined by proliferation assays, and mode of action of cabazitaxel was assessed by western blotting and two screening approaches, i.e. whole proteome analysis and a human apoptosis array.RESULTS: Activity of paclitaxel and cabazitaxel was not affected by cisplatin resistance, suggesting that there is no cross-resistance between these agents in vitro. Cabazitaxel treatment showed a strong inhibitory effect on colony formation capacity. Cabazitaxel induced classical apoptosis in all cell lines, reflected by cleavage of PARP and caspase 3, without inducing specific changes in the cell cycle distribution. Using the proteomic and human apoptosis array screening approaches, differential regulation of several proteins, including members of the bcl-2 family, was found, giving first insights into the mode of action of cabazitaxel in GCT.CONCLUSION: Cabazitaxel shows promising in vitro activity in GCT cells, independent of levels of cisplatin resistance.

AB - BACKGROUND: Cisplatin-based chemotherapy is highly effective in metastasized germ cell tumours (GCT). However, 10-30 % of patients develop resistance to cisplatin, requiring salvage therapy. We investigated the in vitro activity of paclitaxel and the novel taxane cabazitaxel in cisplatin-sensitive and -resistant GCT cell lines.METHODS: In vitro activity of paclitaxel and cabazitaxel was determined by proliferation assays, and mode of action of cabazitaxel was assessed by western blotting and two screening approaches, i.e. whole proteome analysis and a human apoptosis array.RESULTS: Activity of paclitaxel and cabazitaxel was not affected by cisplatin resistance, suggesting that there is no cross-resistance between these agents in vitro. Cabazitaxel treatment showed a strong inhibitory effect on colony formation capacity. Cabazitaxel induced classical apoptosis in all cell lines, reflected by cleavage of PARP and caspase 3, without inducing specific changes in the cell cycle distribution. Using the proteomic and human apoptosis array screening approaches, differential regulation of several proteins, including members of the bcl-2 family, was found, giving first insights into the mode of action of cabazitaxel in GCT.CONCLUSION: Cabazitaxel shows promising in vitro activity in GCT cells, independent of levels of cisplatin resistance.

KW - Journal Article

U2 - 10.1007/s00432-016-2204-6

DO - 10.1007/s00432-016-2204-6

M3 - SCORING: Journal article

C2 - 27424191

VL - 142

SP - 1979

EP - 1994

JO - J CANCER RES CLIN

JF - J CANCER RES CLIN

SN - 0171-5216

IS - 9

ER -