Depression of MAD2 inhibits apoptosis of gastric cancer cells by upregulating Bcl-2 and interfering mitochondrion pathway.

Abstract

Mitotic arrest deficient 2 (MAD2) is an essential component of the mitotic spindle checkpoint pathway. It was previously shown to be associated with drug resistance of tumor cells. To further explore the roles of MAD2 in responses of gastric cancer cells to chemotherapy drugs, we constructed the siRNA vectors of MAD2 and transfected them into gastric cancer SGC7901 cells to inhibit expression of MAD2. MTT assay showed that the downregulation of MAD2 increased the resistance of SGC7901 cells to spindle inhibitors and DNA damaging agents. The apoptosis rates of gastric cancer cells transfected with MAD2-siRNA were 10.7% and 10%, respectively, after treated by 1.0microg/ml VCR and cisplatin. In contrast, the apoptosis rates of SGC7901 and SGC7901/psilencer3.1 induced by VCR were 43.2%, 38.7%; and that induced by cispaltin were 34.1%, 31.4%. The ratio of Bcl-2 to Bax was much higher in the MAD2-siRNA transfectants compared with the SGC7901/psilencer. In SGC7901/psilencer, cytochrome c and cleaved caspase 3 protein levels increased along with the exposure time increased. However, these protein levels of SGC7901/MAD2-siRNA had no changes during the drug treatment. These results indicate that down regulation of MAD2 could promote the drug resistance of gastric cancer cells and inhibit anticancer drugs induced-apoptosis by upregulating Bcl-2 and interfering the mitochondrion apoptosis pathway.

• Authors: Yulei Du, Fang Yin, Changjiang Liu, Shengjuan Hu, Jun Wang, Huahong Xie, Liu Hong, Daiming Fan
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 345 Issue 3 Pg. 1092-8 (Jul 07 2006) ISSN: 0006-291X [Print] United States
• PMID: 16714000 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Calcium-Binding Proteins
• Cell Cycle Proteins
• MAD2L1 protein, human
• Mad2 Proteins
• Proto-Oncogene Proteins c-bcl-2
• Repressor Proteins
• CASP3 protein, human
• Caspase 3
• Caspases
• Cisplatin

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• Calcium-Binding Proteins (genetics, physiology)
• Caspase 3
• Caspases (metabolism)
• Cell Cycle Proteins (genetics, physiology)
• Cell Line, Tumor
• Cisplatin (pharmacology)
• DNA Damage
• Drug Resistance, Neoplasm (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Inhibitory Concentration 50
• Mad2 Proteins
• Mitochondria (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Repressor Proteins (genetics, physiology)
• Stomach Neoplasms (metabolism)