Relationship between multidrug resistant gene expression and multidrug resistant-reversing effect of MS-209 in various tumor cells.
MS-209 is a novel quinoline compound which can overcome multidrug resistance (MDR) both in vitro and in vivo, while having a low level of side effects, and is now being evaluated in a clinical phase II study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantitate the expression levels of MDR genes in various mouse and human tumor cell lines. The MDR gene and the beta actin gene, as the internal reference standard, were coamplified separately, and the relative expression of the MDR gene was represented by the MDR/beta actin ratio. The in vitro MDR-reversing effect of MS-209 was then compared with the MDR gene expression (MDR/beta actin ratio). We found a significant correlation between these two parameters. Moreover, a significant correlation was also observed between the level of expression of the MDR1 gene and that of P-glycoprotein in human cell lines. Therefore, the efficacy of MS-209 seems to specifically depend on the level of MDR gene expression (P-glycoprotein). From these observations, it is suggested that RT-PCR assays of MDR1 gene in tumor biopsy specimens might be an effective means to predict the response of tumor cells to combination therapy with MS-209.
Baba
M
M
Institute of Biological Science, Mitsui Pharmaceuticals, Inc., Chiba, Japan.
Nakanishi
O
O
Sato
W
W
Saito
A
A
Miyama
Y
Y
Yano
O
O
Shimada
S
S
Fukazawa
N
N
Naito
M
M
Tsuruo
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics; D012334:RNA, Neoplasm / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic
D000970:Antineoplastic Agents; D011804:Quinolines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C087719:dofequidar