Actin organization associated with the expression of multidrug resistant phenotype in osteosarcoma cells and the effect of actin depolymerization on drug resistance.
We have previously reported that P-glycoprotein (Pgp)-overexpressing multidrug resistant (MDR) osteosarcoma cells were functionally more differentiated than their parent cells. The present study showed that in the parent cells, the actin filaments were sparsely distributed or were diffusely spread throughout the cytoplasm, whereas the MDR osteosarcoma cells exhibited a remarkable increase in well-organized actin stress fibers. Furthermore, dihydrocytochalasin B, a specific inhibitor of actin polymerization, dramatically disrupted this network of stress fibers, increased the intracellular accumulation of doxorubicin (DOX) and modified the resistance against DOX. These results indicate that the organization of actin filaments associated with cellular differentiation may be involved in the expression of Pgp function in the MDR osteosarcoma cells.
Takeshita
H
H
Department of Orthopaedic Surgery, Kyoto Prefectural University of Medicine, Japan.
Kusuzaki
K
K
Ashihara
T
T
Gebhardt
M C
MC
Mankin
H J
HJ
Hirasawa
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D003571:Cytochalasin B / Q000031:analogs & derivatives / Q000494:pharmacology; D004317:Doxorubicin / Q000378:metabolism; D018432:Drug Resistance, Multiple; D051379:Mice; D012516:Osteosarcoma / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000199:Actins; C024794:dihydrocytochalasin B; D003571:Cytochalasin B; D004317:Doxorubicin