A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma

• Published in: Biochemical and biophysical research communications 2015-12, Vol.468 (4), p.525-532
• Main Authors: Hu, Bo, Sun, Ding, Sun, Chao, Sun, Yun-Fan, Sun, Hai-Xiang, Zhu, Qing-Feng, Yang, Xin-Rong, Gao, Ya-Bo, Tang, Wei-Guo, Fan, Jia, Maitra, Anirban, Anders, Robert A., Xu, Yang
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - chemistry; APOPTOSIS; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - secondary; CELL CYCLE; Cell Line, Tumor; CELL PROLIFERATION; Cell Proliferation - drug effects; CURCUMIN; Curcumin - administration & dosage; Curcumin - chemistry; Diffusion; Drug Synergism; Hepatocellular carcinoma; HEPATOMAS; IN VITRO; IN VIVO; LIVER; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; LUNGS; Male; METASTASES; Mice; Mice, Inbred BALB C; Mice, Nude; MMP-9; Nanocapsules - chemistry; Nanocapsules - ultrastructure; NANOPARTICLES; NF-κB; Niacinamide - administration & dosage; Niacinamide - analogs & derivatives; Niacinamide - chemistry; Phenylurea Compounds - administration & dosage; Phenylurea Compounds - chemistry; Polymers - chemistry; Sorafenib; THERAPY; Treatment Outcome
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.10.031

Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development. •Polymeric nanoparticle formulation of curcumin not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo.•In combination with sorafenib, NanoCurcumin induced HCC cell apoptosis and cell cycle arrest.•NanoCurcumin and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway.•NanoCurcumin and sorafenib significantly decreased the population of CD133-positive HCC cells.