title: Effects of doxorubicin on the sensitivity of L1210 leukemia cells to deformation-associated trauma.
abstract: 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.
authors.affiliation: Department of Experimental Pathology, Roswell Park Memorial Institute, Buffalo, NY 14263.
authors.forename: L
authors.initials: L
authors.lastname: Weiss
authors.forename: R J
authors.initials: RJ
authors.lastname: Bernacki
authors.forename: G
authors.initials: G
authors.lastname: Elkin
authors.forename: M
authors.initials: M
authors.lastname: Hillman
mesh_terms: 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
chemical_list: D004317:Doxorubicin