International Journal of Nanomedicine (May 2019)

In vitro and in vivo mechanism of hepatocellular carcinoma inhibition by beta-TCP nanoparticles

  • Liu L,
  • Dai H,
  • Wu Y,
  • Li B,
  • Yi J,
  • Xu C,
  • Wu X

Journal volume & issue
Vol. Volume 14
pp. 3491 – 3502

Abstract

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Langlang Liu, Honglian Dai, Yanzeng Wu, Binbin Li, Jiling Yi, Chao Xu, Xiaopei WuState Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, People’s Republic of ChinaBackground: Studies have showed that nanoparticles have a certain anti-cancer activity and can inhibit many kinds of cancer cells. β-tricalcium phosphate nanoparticles (nano-β-TCP) displays better biodegradation, but the application and mechanism of nano-β-TCP in anti-cancer activity are still not clear.Purpose: The objective of this study was to synthesize nano-β-TCP and investigate its inhibitory properties and mechanism on hepatocellular carcinoma (HepG2) cells in vitro and in vivo.Methods: Nano-β-TCP was synthesized using ethanol-water system and characterized. The effects of nano-β-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-β-TCP was performed on the xenograft liver cancer model to explore the inhibitory effect and mechanism of nano-β-TCP on liver tumors.Results: In vitro results revealed that nano-β-TCP caused reduced cell viability of HepG2 cells in a time-and dose-dependent manner. Nano-β-TCP was internalized through endocytosis and degraded in cells, resulting in obvious increase of the intracellular Ca2+, and PO43-, ions. Nano-β-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-β-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-β-TCP had no significant toxic side effects, but could effectively suppress hepatocellular carcinoma growth.Conclusion: These findings revealed the anticancer effect of nano-β-TCP and also clarified the mechanism of its inhibitory effect on hepatocellular carcinoma.Keywords: nano-β-TCP, HepG2 cells, ROS, cell cycle, apoptosis, inhibition

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