Nonimmunosuppressant immunophilin ligand GPI-1046 does not promote in vitro growth of prostate cancer cells.
OBJECTIVE
Nonimmunosuppressant immunophilin ligands such as GPI-1046 have gained interest recently for their clinical potential to reduce the extent of injury sustained by penile innervation during radical prostatectomy for prostate cancer treatment and thereby improve erectile function recovery postoperatively. Preclinical studies in rat animal models of cavernous nerve injury have demonstrated that immunophilin ligands exert both neuroprotective and neuroregenerative effects on physiologic erection and on the morphology of erectile tissue and penile innervation. Before establishing their clinical roles, however, it would be useful to evaluate whether they exert mitogenic effects on malignant prostate cells.


METHODS
Human prostate cancer cell lines (LAPC-4, CWR22Rv1, LNCaP, and PC-3) were treated in vitro with 0 to 10 microM of the prototypical nonimmunosuppressant ligand GPI-1046 in 1% fetal bovine serum (FBS)-containing (ie, low growth) media, and their growth was assayed during a 7-day period using spectrophotometric cell counting. The results were normalized for comparison to the maximal growth produced in 10% FBS-containing media.


RESULTS
All four prostate cancer cell lines grew maximally in 10% FBS-containing media, and this growth was reduced by more than twofold (P <0.05) when the cells were maintained in 1% FBS-containing media. The addition of 10 microM or less GPI-1046 to the cells in 1% FBS-containing media did not exert statistically significant mitogenic effects on human prostate cancer cells in vitro.


CONCLUSIONS
These data contribute toward allaying concerns that the use of nonimmunosuppressant immunophilin ligand therapy for the improvement of erectile function recovery after radical prostatectomy will promote recurrent prostate cancer.
Burnett
Arthur L
AL
Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-2411, USA. aburnett@jhmi.edu
Kramer
Melissa F
MF
Dalrymple
Susan
S
Isaacs
John T
JT
D002455:Cell Division / Q000187:drug effects; D006801:Humans; D020104:Immunophilins / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000473:pathology*; D011759:Pyrrolidines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
C104949:GPI 1046; D008024:Ligands; D018696:Neuroprotective Agents; D011759:Pyrrolidines; D020104:Immunophilins