The study was undertaken to investigate the antitumor activity of
DA-125, a promising new analogue of
adriamycin (ADM) containing
fluorine, against human gastric and pulmonary
adenocarcinoma cell lines and their sublines resistant to ADM and
cisplatin (CDDP) by MTT assay. The cells used were MKN-45, human gastric
adenocarcinoma, PC-14, human pulmonary
adenocarcinoma, and their sublines resistant to ADM, MKN/ADM and PC/ADM, and CDDP, MKN/DDP and PC/DDP. MKN/ADM and PC/ADM were 12.6- and 13.9-fold resistant to ADM, respectively, compared to the respective parental cell lines in terms of IC50. The survival was less in cells treated with
DA-125 than that treated with ADM in all lines tested. The antitumor activity of
DA-125 was compared with that of ADM using IC50 values and relative resistance (RR). RR was defined as the ratio of the IC50 value of the resistant subline to that of the parent line. In all lines tested, the mean IC50 values for both
DA-125 and ADM were lowest in the parent cells, followed by CDDP-resistant cells and ADM-resistant cells. The IC50 values for
DA-125 were lower than those for ADM in all six lines tested, although statistical significance was observed in four lines. ADM-resistant sublines were highly resistant to
DA-125 (RRs for ADM and
DA-125; 12.6 and 7.6 MKN/ADM and 13.9 and 10.3 in PC/ADM, respectively). On the other hand, CDDP-resistant sublines were also resistant to ADM and
DA-125 when compared with the respective parent cell lines (RRs for ADM and
DA-125; 2.3 and 2.0 in MKN/DDP and 4.8 and 6.0 in PC/DDP, respectively). Although
DA-125 showed cross-resistance to ADM and CDDP, we recommended
DA-125 to be a good candidate for further development because
DA-125 exhibited remarkable antitumor activity against the parent cell lines.