Reversing multidrug resistance in L1210 tumor cells by hycanthone or chlorophenoxamine in vitro and in vivo.
In the presence study we demonstrated that hycanthone and chlorophenoxamine can modulate the resistance of multidrug resistant (MDR) murine L1210 leukemia tumor lines in vitro and in vivo. The circumvention of MDR by hycanthone and chlorophenoxamine in vitro was demonstrated by a short-term test using tritiated nucleic acid precursors and by flow cytometrical measurement of accumulation of rhodamine 123. Furthermore, we treated mice bearing resistant L1210 ascites cells with doxorubicin and hycanthone or chlorophenoxamine. Hycanthone in combination with doxorubicin significantly inhibited tumor growth. We also found an improved therapeutic effect of doxorubicin plus chlorophenoxamine. Our results in vitro and in vivo indicate that hycanthone and chlorophenoxamine might be appropriate tools for the circumvention of MDR in human tumors.
Efferth
T
T
German Cancer Research Center, Institute of Experimental Pathology, Heidelberg.
Klett
T
T
Mattern
J
J
Osswald
H
H
Pommerenke
E W
EW
Stöhr
M
M
Volm
M
M
D000818:Animals; D004317:Doxorubicin / Q000627:therapeutic use; D004351:Drug Resistance; D005021:Ethylamines / Q000494:pharmacology*; D005434:Flow Cytometry; D006826:Hycanthone / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D005021:Ethylamines; D012235:Rhodamines; D020112:Rhodamine 123; D006826:Hycanthone; C100100:chlorphenoxamine; D004317:Doxorubicin