Chemotherapy with PLGA microspheres containing docetaxel decreases angiogenesis in human hepatoma xenograft.
To investigate the antiangiogenic effect of sustained-release poly (lactic-co-glycolic acid) microspheres containing docetaxel (PMCD) in human hepatoma xenograft. PMCD were prepared by solvent evaporation method with an encapsulation efficiency of 98.7% and a release period of about 3 weeks in vitro. PMCD were intratumorally injected once for mice bearing a human hepatocellular carcinoma. On day 21 post-treatment, the inhibition rate of tumor growth was 72.7% in the high-dose group, indicating a significant antitumor activity. Meanwhile, excellent antiangiogenic effect was observed based on the contrast-enhanced ultrasonography as well as microvessel density determination. Additionally, the real-time fluorescence quantitative PCR revealed that the expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiopoietin-2 (Ang2) genes were down-regulated significantly. Interstitial chemotherapy using PMCD was highly effective and safe for the treatment of the human hepatoma xenograft and that decreasing angiogenesis could be one of the most important mechanisms involved in the antitumor activity.
Department of Ultrasound, Affiliated Union Hospital, Fujian Medical University, 350001 Fuzhou, Fujian, China.
Zhi-kui
ZK
Chen
Min-xian
MX
Cai
Jing
J
Yang
Li-wu
LW
Lin
En-sheng
ES
Xue
Jing
J
Huang
Hong-fen
HF
Wei
Xiu-juan
XJ
Zhang
Li-ming
LM
Ke
D042702:Angiopoietin-2 / Q000096:biosynthesis; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000494:pharmacology; D000077143:Docetaxel; D004337:Drug Carriers; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D060888:Real-Time Polymerase Chain Reaction; D043823:Taxoids / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays
D042702:Angiopoietin-2; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D043823:Taxoids; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid