@Article{096504017X14886444100783,
AUTHOR = {Wenliang Tan, Sicong Zhu, Jun Cao, Lei Zhang, Wenda Li, Kairui Liu, Jinyi Zhong, 
Changzhen Shang, Yajin Chen},
TITLE = {Inhibition of MMP-2 Expression Enhances the Antitumor Effect of Sorafenib  in Hepatocellular Carcinoma by Suppressing the PI3K/AKT/mTOR Pathway},
JOURNAL = {Oncology Research},
VOLUME = {25},
YEAR = {2017},
NUMBER = {9},
PAGES = {1543--1553},
URL = {http://www.techscience.com/or/v25n9/56939},
ISSN = {1555-3906},
ABSTRACT = {Sorafenib has been globally approved as the standard treatment for patients with advanced hepatocellular carcinoma (HCC). However, the response rate of HCC patients to sorafenib is limited because of tumor recurrence 
and metastasis. Therefore, seeking combined therapeutic strategies with sorafenib is necessary to improve 
the antitumor efficiency. Here we demonstrated that expression of MMP-2 is positively correlated with the 
migration ability of HCC cells. Cells with a higher MMP-2 expression (SK-HEP-1 cells) were less sensitive 
to sorafenib than those with lower MMP-2 expression (HepG2 cells). Cotreatment of cells with SB-3CT and 
sorafenib more strongly inhibited migration ability than with sorafenib treatment alone in both HCC cells with 
high and low expression of MMP-2. In vivo cell metastasis experiments confirmed the synergistic effects of 
sorafenib and SB-3CT in reducing lung metastasis of SK-HEP-1 cells. Mechanistically, we showed that the 
synergistic antitumor effect may be attributed to inhibition of the PI3K/AKT/mTOR signaling pathway, but not 
the RAF/MEK/ERK signaling pathway. With these results taken together, the current study demonstrates that 
inhibiting MMP-2 expression can enhance the antitumor effect of sorafenib in HCC cells with a high MMP-2 
expression, which may provide a novel strategy to improve therapeutic efficiency in HCC.},
DOI = {10.3727/096504017X14886444100783}
}