Reversal of the malignant phenotype of gastric cancer cells by inhibition of RhoA expression and activity.

Abstract

PURPOSE:

The small GTPase RhoA has been implicated in the regulation of cell morphology, motility, and transformation, but the role of RhoA protein in the carcinogenesis of gastric cancer remains unclear. In the present study, we have analyzed the expression status of the RhoA protein in human gastric cancer cells and tissues and investigated the possible involvement of RhoA in regulating the malignant phenotype of gastric cancer cells.

EXPERIMENTAL DESIGN:

RhoA expression was analyzed by immunohistochemistry and Western blot in gastric cancer tissues and cell lines. The RhoA-specific small interfering RNA (siRNA) vector was designed and constructed. We examined the role of RhoA in the malignant phenotype of gastric cancer cells by using siRNA knockdown and dominant-negative RhoA mutant suppression of endogenous RhoA activity.

RESULTS:

RhoA was found frequently overexpressed in gastric cancer tissues and cells compared with normal tissues or gastric epithelial cells. RhoA-specific siRNA could specifically and stably reduce RhoA expression up to 90% in AGS cells. Both RhoA-specific siRNA and dominant-negative RhoA expressions could significantly inhibit the proliferation and tumorigenicity of AGS cells and enhance chemosensitivity of the cancer cells to Adriamycin and 5-fluorouracil.

CONCLUSION:

RhoA may play a critical role in the carcinogenesis of gastric cancer, and the interference of RhoA expression and/or activity could provide a novel avenue in reversing the malignant phenotype of gastric cancer cells.

• Authors: Na Liu, Feng Bi, Yanglin Pan, Lijun Sun, Yan Xue, Yongquan Shi, Xuebiao Yao, Yi Zheng, Daiming Fan
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 18 Pt 1 Pg. 6239-47 (Sep 15 2004) ISSN: 1078-0432 [Print] United States
• PMID: 15448013 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Antimetabolites, Antineoplastic
• Antineoplastic Agents
• Oligonucleotides
• RNA, Small Interfering
• Tetrazolium Salts
• Thiazoles
• Doxorubicin
• Agar
• DNA
• rhoA GTP-Binding Protein
• thiazolyl blue
• Fluorouracil

Topics

• Agar (chemistry)
• Animals
• Antibiotics, Antineoplastic (pharmacology)
• Antimetabolites, Antineoplastic (pharmacology)
• Antineoplastic Agents (pharmacology)
• Blotting, Western
• Cell Cycle
• Cell Differentiation
• Cell Line, Transformed
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• DNA (metabolism)
• Disease Progression
• Dose-Response Relationship, Drug
• Doxorubicin (pharmacology)
• Epithelial Cells (metabolism)
• Flow Cytometry
• Fluorouracil (pharmacology)
• Genes, Dominant
• Humans
• Immunohistochemistry
• Mice
• Mutation
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Oligonucleotides (chemistry)
• Phenotype
• RNA, Small Interfering (metabolism)
• Stomach Neoplasms (drug therapy, pathology)
• Tetrazolium Salts (pharmacology)
• Thiazoles (pharmacology)
• Time Factors
• Transfection
• Wound Healing
• rhoA GTP-Binding Protein (antagonists & inhibitors, metabolism)