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

Masanobu Tsubaki; Takao Satou; Tatsuki Itoh; Motohiro Imano; Makiko Komai; Minori Nishinobo; Megumi Yamashita; Masashi Yanae; Yuzuru Yamazoe; Shozo Nishida

doi:10.1016/j.leukres.2012.07.003

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

Leuk Res. 2012 Oct;36(10):1315-22. doi: 10.1016/j.leukres.2012.07.003. Epub 2012 Jul 19.

Authors

Masanobu Tsubaki¹, Takao Satou, Tatsuki Itoh, Motohiro Imano, Makiko Komai, Minori Nishinobo, Megumi Yamashita, Masashi Yanae, Yuzuru Yamazoe, Shozo Nishida

Affiliation

¹ Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka 577-8502, Japan.

PMID: 22819074
DOI: 10.1016/j.leukres.2012.07.003

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
Apoptosis / drug effects
Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / 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
Inhibitor of Apoptosis Proteins / genetics
Inhibitor of Apoptosis Proteins / metabolism*
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Multiple Myeloma / drug therapy*
Multiple Myeloma / genetics
Multiple Myeloma / metabolism*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism*
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Real-Time Polymerase Chain Reaction
Survivin
Tumor Cells, Cultured
Verapamil / pharmacology

Substances

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