. Author manuscript; available in PMC: 2015 Aug 5.

Published in final edited form as: Nat Rev Gastroenterol Hepatol. 2014 Sep 30;11(12):750–761. doi: 10.1038/nrgastro.2014.155

Table 4.

Preclinical studies in animal models of polycystic liver diseases

Study	Drug	Animal model	Treatment	Results
cAMP
Masyuk et al. (2007)⁹⁷	Octreotide	PCK rat	Intraperitoneally (10μg/kg daily) for 4, 8, 12, and 16 weeks or 100μg/kg daily for 4 weeks	Reduction of liver weight, cyst volume, hepatic fibrosis, and mitotic indices
Masyuk et al. (2013)⁹⁹	Pasireotide	PCK rat and Pkd2^WS25/− mouse	Osmotic mini-pumps (20 μg/kg daily) for 6 weeks	Reduction of liver weight, cyst volume, hepatic fibrosis and mitotic indices
Raf kinase
Spirli et al. (2012)⁸⁹	Sorafenib	Pkd2^fox/−:pCxCreER™ (Pkd2cKO mouse)	Orally (20–60 mg/kg daily) for 8 weeks	Increase in liver cyst area, cell proliferation and phosphorylated Erk
*mTOR*
Spirli et al. (2010)⁷³	Sirolimus	Pkd2^fox/−:pCxCreER™ (Pkd2cKO mouse)	Intraperitoneally (1.5 mg/kg daily) for 8 weeks	Reduction of liver cyst area, liver weight and Pcna expression
Renken et al. (2011)⁸⁴	Sirolimus	PCK rat	In drinking water (2 mg/kg daily) for 4, 8 or 12 weeks	Failed to attenuate hepatorenal cystogenesis
*Cdc25A*
Masyuk et al. (2012)⁷⁵	Vitamin K3	Pkd2^WS25/− mouse and PCK rat	In drinking water (0.15 g/l) for 4 and 8 weeks	Reduction of both liver and kidney weights and hepatorenal cystic and fibrotic areas
Masyuk et al. (2012)⁷⁵	PM-20	Pkd2^WS25/− mouse	Intraperitoneally (1 mg/kg) for 4 weeks	Reduction of hepatorenal cystogenesis
*MMPs*
Urribarri et al. (2014)¹¹⁴	Marimastat	PCK rat	Orally twice a day (0.29 mg/kg daily) for 8 weeks	Reduction of hepatic cystogenesis, fibrosis and inflammation
*Hdac6*
Gradilone et al. (2014)¹¹⁹	ACY-1215	PCK rat	Intraperitoneally (30 mg/kg daily) for 4 weeks	Reduction of hepatic cystogenesis and fibrosis
*Ppar-γ*
Yoshihara et al. (2011)⁹⁰	Pioglitazone (full agonist)	PCK rat	Orally (10 mg/kg daily) for 16 weeks	Reduction of liver weight, liver cystic area and fibrotic index
Yoshihara et al. (2013)⁹²	Telmisartan (partial agonist)	PCK rat	Orally (3 mg/kg daily) for 16 weeks	Reduction of liver weight, cystic and fibrotic areas
*Vegfr2*
Spirli et al. (2010)⁷⁴	SU5416	Pkd1KO and Pkd2KO mice	Intraperitoneally (12.5 mg/kg) twice a week for 8 weeks	Reduction of hepatic cystogenesis, liver weight and levels of phosphorylated Erk and Pcna in Pkd2KO but not Pkd1KO mice
Amura et al. (2007)⁸²	SU5416	Pkd2^WS25/ mouse	Subcutaneously (0.75 mg) every 2 weeks for 4 and 8 months	Reduction of liver cystic area
*Egfr*
Torres et al. (2004)⁸¹	EKI-785 and EKB-569	PCK rat	Intraperitoneally (EKI-785: 90 mg/kg) every 3 days Intraperitoneally (EKB-569: 20 mg/kg) every 3 days Orally (EKB-569: 5, 10 or 20 mg/kg) every 3 days All administered for 7 weeks	No effects on fibrocystic liver disease
*Trpv4*
Gradilone et al. (2010)⁶⁵	Trpv4 activator GSK1016790A	PCK rat	Intraperitoneally (0.01 mg/kg daily) for 8 weeks	Trpv4 activation induced a significant decrease in renal cystic area and a nonsignificant decrease in liver cysts

Abbreviations: cAMP, cyclic adenosine monophosphate; Cdc25A, cyclin division cycle 25A; Egfr, epidermal growth factor receptor; Erk, extracellular-regulated kinase; Hdac6, histone deacetylase 6; MMP, matrix metalloprotease; mTOR, mammalian target of rapamycin; Pcna, proliferating cell nuclear antigen; PPAR-y, peroxisome proliferator-activated receptor gamma; Raf, rapidly accelerated fibrosarcoma; Trpv4, transient receptor potential cation channel, subfamily V, member 4; Vegfr2, vascular endothelial growth factor receptor 2.