ABSTRACT
Background: Studies have showed that nanoparticles have a certain anti-cancer activity and can inhibit many kinds of cancer cells. ß-tricalcium phosphate nanoparticles (nano-ß-TCP) displays better biodegradation, but the application and mechanism of nano-ß-TCP in anti-cancer activity are still not clear. Purpose: The objective of this study was to synthesize nano-ß-TCP and investigate its inhibitory properties and mechanism on hepatocellular carcinoma (HepG2) cells in vitro and in vivo. Methods: Nano-ß-TCP was synthesized using ethanol-water system and characterized. The effects of nano-ß-TCP on cell viability, cell uptake, intracellular oxidative stress (ROS), cell cycle and apoptosis were also investigated with HepG2 cells and human hepatocyte cells (L-02). Intratumoral injection of nano-ß-TCP was performed on the xenograft liver cancer model to explore the inhibitory effect and mechanism of nano-ß-TCP on liver tumors. Results: In vitro results revealed that nano-ß-TCP caused reduced cell viability of HepG2 cells in a time-and dose-dependent manner. Nano-ß-TCP was internalized through endocytosis and degraded in cells, resulting in obvious increase of the intracellular Ca2+ and PO4 3- ions. Nano-ß-TCP induced cancer cells to produce ROS and induced apoptosis of tumor cells by an apoptotic signaling pathways both in extrinsic and intrinsic pathway. In addition, nano-ß-TCP blocked cell cycle of HepG2 cells in G0/G1 phase and disturbed expression of some related cyclins. In vivo results showed that 40 mg/kg of nano-ß-TCP had no significant toxic side effects, but could effectively suppress hepatocellular carcinoma growth. Conclusion: These findings revealed the anticancer effect of nano-ß-TCP and also clarified the mechanism of its inhibitory effect on hepatocellular carcinoma.
