Effects of vinblastine on cell membrane fluidity and the growth of SA-1 tumor in mice.
Cell membranes can be targets of some anti-cancer drugs. Therefore, the purpose of this study was to determine whether vinblastine (VLB) can also affect the tumor cell membrane. On the in vivo SA-1 tumor model, alteration of cell membrane fluidity (measured by electron paramagnetic resonance, EPR), cytotoxicity and morphological changes of the SA-1 tumor cells after VLB treatment were studied. The cytotoxic effect of VLB was biphasic, with an initial fast increase in cytotoxicity followed by a plateau. The surviving cells had increased membrane fluidity and were morphologically changed. The dose-response curve of VLB on membrane fluidity was also biphasic with an initial fast increase in membrane fluidity followed by a plateau. Since dose-response curves of VLB cytotoxicity and its effect on membrane fluidity were similar, there was a high correlation between both effects. The effect of VLB on membrane fluidity was the most pronounced at 24 h and 48 h after treatment. The results of this study indicate that VLB affects cell membrane by increasing the membrane fluidity of SA-1 tumor cells in vivo in a dose-and time-dependent manner. Therefore, this finding may be beneficially implemented also in priming cells for other cytotoxic drugs and for appropriate timing of drug sequence in combined schedules.
Sersa
G
G
Institute of Oncology, Ljubljana, Slovenia.
Cemazar
M
M
Sentjurc
M
M
Us-Krasovec
M
M
Kalebić
S
S
Draslar
K
K
Auersperg
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D005354:Fibrosarcoma / Q000473:pathology* / Q000648:ultrastructure; D008560:Membrane Fluidity / Q000187:drug effects*; D051379:Mice; D008805:Mice, Inbred A; D008855:Microscopy, Electron, Scanning; D012513:Sarcoma, Experimental / Q000473:pathology* / Q000648:ultrastructure; D013997:Time Factors; D014747:Vinblastine / Q000633:toxicity*
D014747:Vinblastine