JK184 can specially inhibit Gli in the Hedgehog (Hh) pathway, which showed great promise for
cancer therapeutics. For developing aqueous formulation and improving anti-
tumor activity of
JK184, we prepared
JK184 encapsulated
MPEG-PCL micelles by the solid dispersion method without using
surfactants or toxic organic
solvents. The cytotoxicity and cellular uptake of
JK184 micelles were both increased compared with the free
drug.
JK184 micelles induced more apoptosis and blocked proliferation of Panc-1 and BxPC-3
tumor cells. In addition,
JK184 micelles exerted a sustained in vitro release behavior and had a stronger inhibitory effect on proliferation, migration and invasion of HUVECs than free
JK184. Furthermore,
JK184 micelles had stronger
tumor growth inhibiting effects in subcutaneous Panc-1 and BxPC-3
tumor models. Histological analysis showed that
JK184 micelles improved anti-
tumor activity by inducing more apoptosis, decreasing microvessel density and reducing expression of CD31, Ki67, and
VEGF in
tumor tissues.
JK184 micelles showed a stronger inhibition of Gli expression in Hh signaling, which played an important role in
pancreatic carcinoma. Furthermore, circulation time of
JK184 in blood was prolonged after entrapment in polymeric
micelles. Our results suggested that
JK184 micelles are a promising
drug candidate for treating pancreatic
tumors with a highly inhibitory effect on Hh activity.