ABSTRACT
Scavenger receptor class B type 1 (SR-B1) is over-expressed in tumour cells where it mediates the uptake of drug payload of reconstituted high density lipoprotein (rHDL) via the process of reverse cholesterol transport. In this study, rHDL was prepared to determine its function as a drug delivery carrier for targeting hepatocellular carcinoma by incorporating the anti-tumour drug garcinia glycosides (GG) into rHDL to yield rHDL/GG nano-complexes. Structural analysis indicated that the rHDL/GG nano-complex was similar to HDL in size. HepG2 cells treated with fluorescent-labelled rHDL/GG exhibited a time-dependent increase in cell death. Further experiment in which HepG2 cells were treated with rHDL/GG plus plasma-derived HDL showed reduction in cell death compared to treatment with rHDL/GG alone, suggesting that plasma-derived HDL compete with rHDL/GG for binding to the SR-B1 on the cell. We concluded that rHDL could not only incorporate GG but could also serve as a carrier, targeting the drug to HepG2 cells via SR-B1.
Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Drug Carriers/chemistry , Garcinia/chemistry , Glycosides/administration & dosage , Lipoproteins, HDL/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Carcinoma, Hepatocellular/drug therapy , Cell Death/drug effects , Drug Delivery Systems , Glycosides/chemistry , Glycosides/pharmacology , Hep G2 Cells , Humans , Liver Neoplasms/drug therapy , Recombinant Proteins/chemistryABSTRACT
Objective To evaluated the inhibitory effect of garcinia glycosides on growth of 8 kinds of human tumor cells in vi-vo by hollow fiber assay and confirm the reliability of hollow fiber assay in anticancer effect by the nude mice xenograft test .Methods Hollow fibers containing tumor cells were inserted underneath the skin of the NOD /SCID mice.The fibers were collected from the mice on the day after the administration and subjected to the stable endpoint MTT assay .The tumor cells of HL-60 and B16 were subcutane-ously implanted into the right flank of BALb /c nude mice.The positive control group was treated with cyclophosphamide .Each group was administered for 10 days.24 hours after the last administration , the mice were sacrificed and the tumors were excised and weigh-ted, the inhibition rate of tumor growth was calculated .Results The high-dose group of 8 mg/( kg· d) , middle dose group of 4 mg/( kg· d) of garcinia glycosides were measured by hollow fiber assay and nude mice test significantly inhibited the in vivo growth of HL -60 and B16 comparing with those in the solvent control group (P<0.01).Conclusion As a new model by hollow fiber assay to evalu-ate the inhibitory effect of garcinia glycosides , the test results were basically the same with nude mice test results .It made the experi-ment more rapidly , accurately and economically .An instruction and reliable evidence for follow-up study of garcinia glycosides was provided in this study .
