Antitumor activity of DA-125, a novel anthracycline, in human gastric and pulmonary adenocarcinoma cells resistant to adriamycin and cisplatin.
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.
Hong
W S
WS
Department of Internal Medicine, Asan Medical Center, University of Ulsan, Seoul, Korea.
Jung
H Y
HY
Yang
S K
SK
Kim
H R
HR
Min
Y I
YI
D000230:Adenocarcinoma / Q000188:drug therapy*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D013274:Stomach Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; C090816:7-O-(2,6-Dideoxy-2-fluoro-alpha-talopyranosyl)adriamycinone- 14-beta-alaniate hydrochloride; D004317:Doxorubicin