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Liposomal gemcitabine (GemLip)—efficient drug against hormone‐refractory Du145 and PC‐3 prostate cancer xenografts
Author(s) -
Jantscheff Peter,
Esser Norbert,
Graeser Ralph,
Ziroli Vittorio,
Kluth Jessica,
Unger Clemens,
Massing Ulrich
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20964
Subject(s) - du145 , gemcitabine , medicine , prostate cancer , prostate , oncology , drug , refractory (planetary science) , liposome , cancer , urology , pharmacology , biology , biochemistry , astrobiology , lncap
BACKGROUND Gemcitabine (Gemc) is an efficient chemotherapeutic drug in various cancer types (e.g., pancreas) but has only limited effects on hormone‐refractory prostate cancer (HRPCa). Since HRPCa cells are highly sensitive to even low doses of Gemc in vitro, the lack of clinical effects might be due to rapid degradation of Gemc by deaminases combined with impaired accumulation in tumor tissue and PCa cells. Liposomal formulation (GemLip) is expected to protect the entrapped cytotoxic substance from enzymatic degradation and furthermore augment its accumulation within tumor tissues due to an enhanced permeability of the tumor vessels. METHODS Anti‐tumoral and anti‐metastatic activity of GemLip and Gemc were investigated in two luciferase‐expressing, human hormone‐refractory PC‐3 and Du145 HRPCa xenograft models in immunodeficient mice. Tumor growth was monitored by in vivo luminescence imaging (orthotopic) or callipering (subcutaneous). Anti‐metastatic effects of treatment were determined by in vitro luciferase assay of the tissues. RESULTS Tumor growth of subcutaneous Du145 xenografts was significantly inhibited only by GemLip (8 mg/kg: P = 0.014 and 6 mg/kg: P = 0.011) but not by conventional Gemc (360 mg/kg). In contrast, growth of orthotopic PC‐3 xenografts was significantly inhibited by both, GemLip ( P = 0.041) and Gemc ( P = 0.002). The drugs furthermore strongly reduced spleen and liver metastases in this model. CONCLUSIONS As shown by the very low efficient concentration of GemLip, liposomal entrapment of Gemc greatly enhances its activity. GemLip has, even at very low doses, a significant anti‐tumoral and anti‐metastatic therapeutic effect in HRPCa xenografts in vivo and was beneficial even when the conventional Gemc failed. Prostate 69:1151–1163, 2009. © 2009 Wiley‐Liss, Inc.