Regulation of multidrug resistance by MGr1-antigen in gastric cancer cells.

Abstract

Previously, a novel protein, MGr1-Ag, was associated with tumor multidrug resistance (MDR), and the role and the underlying mechanisms of MGr1-Ag in MDR of gastric cancer cells were characterized. Initial studies using the introduction of sense or antisense vectors for MGr1-Ag resulted in the genetical up- or downregulation of MGr1-Ag in gastric cancer cells, respectively. Subsequent studies revealed the expression of MGr1-Ag, P-glycoprotein (P-gp), MDR-associated protein (MRP), Bcl-2 and Bax in gastric cancer cells via Western blot analysis. The sensitivity of gastric cancer cells to chemotherapeutic drugs was assessed using the colony-forming assay, and Adriamycin (ADM) accumulation was evaluated by flow cytometry. Further study of ADM-induced apoptosis was detected by annexin-V/propidium iodide staining. The expression level of MGr1-Ag in MDR gastric cancer cells is much higher than that in their parental cells. Overexpression of exogenous MGr1-Ag may promote the MDR phenotype of gastric cancer cells, decrease intracellular ADM accumulation and protect gastric cancer cells from ADM-induced apoptosis, whereas downregulation of MGr1-Ag had reverse effects. Western blot analysis suggested that MGr1-Ag may regulate the expression of P-gp, MRP, Bcl-2 and Bax. In conclusion, MGr1-Ag may promote MDR of gastric cancer cells via a decrease in intracellular drug accumulation and inhibition of drug-induced apoptosis.

• Authors: Li Sun, Yongquan Shi, Changcun Guo, Liping Yao, Tao Lin, Jingping Du, Quanli Han, Ying Han, Daiming Fan
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 27 Issue 1 Pg. 27-35 ( 2006) ISSN: 1010-4283 [Print] Netherlands
• PMID: 16340247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2006 S. Karger AG, Basel.

Chemical References

• Antibiotics, Antineoplastic
• Antigens, Neoplasm
• MGr1-antigen, human
• Doxorubicin

Topics

• Antibiotics, Antineoplastic (pharmacokinetics, pharmacology)
• Antigens, Neoplasm (biosynthesis, physiology)
• Apoptosis (drug effects)
• Blotting, Western
• Down-Regulation
• Doxorubicin (pharmacokinetics, pharmacology)
• Drug Resistance, Multiple (genetics)
• Flow Cytometry
• Humans
• Phenotype
• Stomach Neoplasms (genetics, pathology)
• Tumor Cells, Cultured