[Suppression of hepatocellular carcinoma invasion and metastasis by Rho-kinase inhibitor Fasudil through inhibition of BTBD7-ROCK2 signaling pathway].

Abstract

OBJECTIVE:

To explore the eff ect of Fasudil on the invasion and metastatic abilities of human high metastatic liver cancer cells (HCCLM3) and the underlying mechanisms.

METHODS:

HCCLM3 cells were incubated with 100 μmol/L Fasudil. Fluorescence staining for F-actin and Transwell assay were performed to observe the invasion ability of HCCLM3 cells. HCCLM3 cells were divided into 3 groups: a negative control group, a Fasudil group and a BTB/ POZ domain containing 7 (BTBD7)-siRNA group. Western blot assay was performed to detect the expression levels of BTBD7, ras homolog family member C (RhoC) and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2), matrix metalloproteinases 2 (MMP2) and MMP9. Zymogram analysis method was performed to detect the expression activities of MMP2 and MMP9. The BTBD7-siRNA group was served as a positive control.

RESULTS:

In HCCLM3 cells treated with Fasudil, the invasion ability was significant decreased compared with the control group, concomitant with the down-regulated expression levels of BTBD7, RhoC and ROCK2 protein as well as the decreased activities of MMP2 and MMP9.

CONCLUSION:

Fasudil plays an important role in interfering BTBD7-ROCK2 signaling pathway and suppressing the invasion and metastasis of hepatocellular carcinoma.

• Authors: Kuan Hu, Zhiming Wang, Yiming Tao
• Journal: Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences (Zhong Nan Da Xue Xue Bao Yi Xue Ban) Vol. 39 Issue 12 Pg. 1221-7 (Dec 2014) ISSN: 1672-7347 [Print] China
• PMID: 25544168 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• BTBD7 protein, human
• Neoplasm Proteins
• RNA, Small Interfering
• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
• ROCK2 protein, human
• rho-Associated Kinases
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9
• fasudil

Topics

• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (analogs & derivatives, pharmacology)
• Adaptor Proteins, Signal Transducing
• Carcinoma, Hepatocellular (metabolism, pathology)
• Cell Line, Tumor (drug effects)
• Cell Movement
• Down-Regulation
• Humans
• Liver Neoplasms (metabolism, pathology)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Neoplasm Invasiveness
• Neoplasm Proteins (metabolism)
• Neoplasms, Second Primary
• RNA, Small Interfering
• Signal Transduction
• rho-Associated Kinases (antagonists & inhibitors, metabolism)