Regulation of multidrug resistance by MGr1-antigen in gastric cancer cells.
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.
Sun
Li
L
State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Shi
Yongquan
Y
Guo
Changcun
C
Yao
Liping
L
Lin
Tao
T
Du
Jingping
J
Han
Quanli
Q
Han
Ying
Y
Fan
Daiming
D
D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D015536:Down-Regulation; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005434:Flow Cytometry; D006801:Humans; D010641:Phenotype; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000951:Antigens, Neoplasm; C470229:MGr1-antigen, human; D004317:Doxorubicin