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Asiaticoside Antagonizes Proliferation and Chemotherapeutic Drug Resistance in Hepatocellular Carcinoma (HCC) Cells

Ying Ma, Jun Wen, Jing Wang, Chunyan Wang, Yan Zhang, Lili Zhao, Jia Li, Xue Feng

Second Department of Hepatopathy, Tianjin Second People’s Hospital, Tianjin, China (mainland)

Med Sci Monit 2020; 26:e924435

DOI: 10.12659/MSM.924435

Available online: 2020-06-29

Published: 2020-08-30

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most prevalent malignant tumor in China after lung cancer, gastric cancer, esophageal cancer, and breast cancer, and has a high mortality rate. Though there are a series of therapeutic strategies is now available for HCC in clinical practice, the 5-year survival rate after surgery is still low. In addition, multi-drug resistance (MDR) is one of the most important factors responsible for the low survival rate and poor therapy response in HCC. Hence, novel treatment strategies and molecules for HCC need to be developed.
MATERIAL AND METHODS: We assessed the effect of asiaticoside, a natural product derived from Centella asiatica (L.) Urban, on HCC cell proliferation and drug resistance.
RESULTS: Our data indicated that asiaticoside significantly inhibited the proliferation of HCC cell lines QGY-7703 and Bel-7402 in a dose- and time-dependent manner. Moreover, asiaticoside significantly induced apoptosis in QGY-7703 and Bel-7402 cells. Treatment with asiaticoside also caused G1 cell cycle arrest in QGY-7703 and Bel-7402 cells. Western blot assay results indicated that the mechanism underlying the effects of asiaticoside involves inhibiting the activity of the PI3K/Akt and MAPK/ERK pathways. Furthermore, asiaticoside significantly antagonized P-gp-mediated MDR in HCC cells.
CONCLUSIONS: Our results suggest that asiaticoside has the potential to be applied in the treatment of HCC patients, but further evidence is needed to confirm our results, particularly in vivo efficacy.

Keywords: Apoptosis, Carcinoma, Hepatocellular, cell cycle checkpoints