Effects of doxorubicin on the sensitivity of L1210 leukemia cells to deformation-associated trauma.
Most of the cancer cells arrested in the microcirculation during hematogenous metastasis are rapidly killed; one major mechanism is surface-membrane rupture, associated with the mechanical deformation of cancer cells in capillaries. The feasibility of increasing the susceptibility of cancer cells to lethal, deformation-associated trauma by doxorubicin, was tested in an in vitro mechanical model system, by filtering suspensions of L1210 leukemia cells through 8-microns pore-size Nuclepore membranes, with or without prior incubation with 10(-7)M doxorubicin. The results showed that mechanically-induced loss of cancer cells immediately after filtration was increased from 18 to 55% in cells previously exposed to doxorubicin for 48 h. The results indicate the feasibility of chemotherapeutic enhancement of the mechanical killing-action of the microvasculature as a potential rate-regulator of hematogenous metastasis.
Weiss
L
L
Department of Experimental Pathology, Roswell Park Memorial Institute, Buffalo, NY 14263.
Bernacki
R J
RJ
Elkin
G
G
Hillman
M
M
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005069:Evaluation Studies as Topic; D005374:Filtration; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D009362:Neoplasm Metastasis; D013314:Stress, Mechanical; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D004317:Doxorubicin