Simultaneous assessment of migration and proliferation of murine fibrosarcoma cells, as affected by hydroxyurea, vinblastine, cytochalasin B, Razoxane and interferon.
Using porous cell culture chambers, we have simultaneously assessed growth and locomotion of cancer cells to investigate whether certain agents affect cell motility in addition to cell division. First, cells from a murine fibrosarcoma cell line, 1.0/L1, were grown in ordinary flask cultures to determine appropriate cell inocula. Doses of agents were selected to reduce the final 4 day culture cellularity to about 50%, when present during the last two days of culturing. Secondly, the effects of these agents on cell numbers in the porous chambers and on cell migration out of the chambers ('emigration fraction') were recorded. We also examined, using a similar type of porous chamber, whether the agents could affect leucocyte chemotaxis. Hydroxyurea (an inhibitor of DNA synthesis) reduced cancer cell emigration as well as cell growth, without interfering with leucocyte chemotaxis. Cytochalasin B (a microfilament disrupting agent) inhibited cancer cell motility and growth, as well as leucocyte chemotaxis. Vinblastine (a microtubule disrupting agent), at the very low dose chosen, reduced cancer cell growth, but did not consistently affect the migration of either cell type. The experimental anti-metastasis agent Razoxane reduced growth, but had no detectable effects on motility. High doses of natural murine interferon-alpha/beta weakly inhibited both cancer cell growth and locomotion. This motivates for further studies of these and other cytokines, as treatment with agents inhibiting cancer cell locomotion might possibly prevent peri-operative spread of cancer in patients.
Haug
I J
IJ
Department of Physiology, Rikshospitalet, University of Oslo, Norway.
Siebke
E M
EM
Grimstad
I A
IA
Benestad
H B
HB
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control; D011929:Razoxane / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014747:Vinblastine / Q000494:pharmacology
D000970:Antineoplastic Agents; D003571:Cytochalasin B; D011929:Razoxane; D014747:Vinblastine; D007372:Interferons; D006918:Hydroxyurea