Effects of Vinblastine and 5-Fluorouracil on Human Glioma and Thyroid Cancer Cell Monolayers and Spheroids1

The effects of the two antitumor drugs vinblastine and 5fluorouracil on the growth of the human tumor cell lines U-118 MG (glioma) and HTh-7 (thyroid cancer) were analyzed. The cells were cultured both as monolayers and as multicellular spheroids and exposed to vinblastine (0.1,1.0, or 10 t¿g/m\) or 5-fluorouracil (10, 100, or 1000 u.g/m\) for 15 min, 2 hr, or 24 hr. The drugs induced growth delays of the monolayers and delays in the outgrowth of cells from spheroids which were placed on celladhesive surfaces. Cell cultures exposed to sublethal drug doses showed a dose-dependent lag period followed by regrowth at normal growth rates. In all cases with vinblastine exposures, the spheroids seemed more resistant to the drug treatments than did the monolayer cultures. Much smaller differences were ob tained after treatments with 5-fluorouracil. The three-dimensional arrangement of cells in spheroids giving rise to, e.g., nutrient and proliferation gradients may, to some extent, be responsible for the increased resistance. The spheroids were especially resistant to short treatments with vinblastine. This was probably due to penetration barriers.