Cytotoxicity of CPT-11 against a Taxol-resistant cell line

We examined the cytotoxic changes of CPT-11 (SN-38) against a Suit-2 cell line after a long-term culture (more than 4 passages) with Taxol (Taxol-resistant cells). The percentage survival of the Suit-2 cells with and without resistance to 0.8 microM Taxol were 20% and 96%, respectively, after treatment with 0.1 microM Taxol for 24 hours. When Suit-2 cells resistant to 0.6, 0.8, and 1.0 yM of Taxol were treated with 15 pM SN-38 for 2 hours, the percentages of survival were 59%, 72%, and 62%, respectively, and no statistical difference was observed with the percentage survival (77%) of Suit-2 cells cultured without Taxol (parent cells). Moreover, Taxol-resistant cells did not cause an inhibition of the relaxation of DNA by topoisomerase I. Therefore, the cytotoxic level of SN-38 between Suit-2 cells with and without resistance to Taxol was almost equal. The percentage survival of SN-38-resistant Suit-2 cells decreased markedly with the increase in the dose of Taxol, and no statistical difference was observed in comparison to that of the parent Suit-2 cells. These results thus indicated that the cross-resistance to SN-38 and Taxol would therefore be very difficult to induce in Suit-2 cells.