Combination of Matrine and Sorafenib Decreases the Aggressive Phenotypes of Hepatocellular Carcinoma Cells.

Abstract

BACKGROUND:

The aim of this study was to determine the effects of matrine (a natural alkaloid) on sorafenib-induced cytotoxicity against hepatocellular carcinoma (HCC) cells, and to explore the molecular mechanisms involved.

METHODS:

HepG2 and Hep3B cells were treated with matrine alone or in combination with sorafenib, and cell viability and apoptosis were assessed. The involvement of micro (mi)RNA-21 in the action of matrine was examined.

RESULTS:

Matrine significantly augmented the antiproliferative activity of sorafenib in a dose-dependent manner. Matrine significantly increased apoptosis, coupled with enhanced cleavage of caspase-3 and poly (ADP-ribose) polymerase. miRNA-21-overexpressing HCC cells showed a marked decrease in matrine-induced growth suppression and the expression of phosphatase and tensin homolog (PTEN). The suppressive effect of combining matrine and sorafenib was significantly reduced by miRNA-21 overexpression or PTEN inhibition.

CONCLUSION:

Matrine in combination with sorafenib leads to increased cytotoxic effects against HCC cells, at least partially, via the suppression of miRNA-21 and the subsequent induction of PTEN.

• Authors: Yan Lin, Lianjie Lin, Yu Jin, Ying Zhang, Dongxu Wang, Yue Tan, Changqing Zheng
• Journal: Chemotherapy (Chemotherapy) Vol. 60 Issue 2 Pg. 112-118 ( 2014) ISSN: 1421-9794 [Electronic] Switzerland
• PMID: 25721136 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel

Chemical References

• Alkaloids
• Antineoplastic Agents
• Phenylurea Compounds
• Quinolizines
• Niacinamide
• Sorafenib
• Matrines

Topics

• Alkaloids (administration & dosage)
• Antineoplastic Agents (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Apoptosis (drug effects, physiology)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Cell Proliferation (drug effects, physiology)
• Dose-Response Relationship, Drug
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Niacinamide (administration & dosage, analogs & derivatives)
• Phenotype
• Phenylurea Compounds (administration & dosage)
• Quinolizines (administration & dosage)
• Sorafenib
• Matrines