Overexpression of MDR1 and survivin, and decreased Bim expression mediate multidrug-resistance in multiple myeloma cells.

Abstract

Multidrug resistance represents a major obstacle for the chemotherapy of a wide variety of human tumors. To investigate the underlying mechanisms associated with resistance to anti-cancer drugs, we established anti-cancer drug-resistant multiple myeloma (MM) cell lines RPMI8226/ADM, RPMI8226/VCR, RPMI8226/DEX, and RPMI8226/L-PAM, the 50% inhibitory concentration values of which were 77-, 58-, 79-, and 30-fold higher than their parental cell lines, respectively. The resistant cell lines overexpressed MDR1 and survivin, or showed decreased Bim expression. These results indicated that regulating these factors with inhibitors might be a viable approach to increasing the susceptibility of quiescent MM cells to chemotherapy.

• Authors: Masanobu Tsubaki, Takao Satou, Tatsuki Itoh, Motohiro Imano, Makiko Komai, Minori Nishinobo, Megumi Yamashita, Masashi Yanae, Yuzuru Yamazoe, Shozo Nishida
• Journal: Leukemia research (Leuk Res) Vol. 36 Issue 10 Pg. 1315-22 (Oct 2012) ISSN: 1873-5835 [Electronic] England
• PMID: 22819074 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Apoptosis Regulatory Proteins
• BCL2L11 protein, human
• BIRC5 protein, human
• Bcl-2-Like Protein 11
• Calcium Channel Blockers
• Inhibitor of Apoptosis Proteins
• Membrane Proteins
• Proto-Oncogene Proteins
• RNA, Messenger
• RNA, Small Interfering
• Survivin
• Verapamil
• Caspases

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics, metabolism)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Bcl-2-Like Protein 11
• Blotting, Western
• Calcium Channel Blockers (pharmacology)
• Caspases (metabolism)
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Humans
• Inhibitor of Apoptosis Proteins (antagonists & inhibitors, genetics, metabolism)
• Membrane Proteins (genetics, metabolism)
• Multiple Myeloma (drug therapy, genetics, metabolism)
• Proto-Oncogene Proteins (genetics, metabolism)
• RNA, Messenger (genetics)
• RNA, Small Interfering (genetics)
• Real-Time Polymerase Chain Reaction
• Survivin
• Tumor Cells, Cultured
• Verapamil (pharmacology)