[Molecular biological evidence for the genetic stability of in vivo passaged doxorubicin resistant cell line S-180R].
OBJECTIVE
To assess the genetic stability of doxorubicin resistant sarcoma 180 cell line(S-180R) after in vivo passages.


METHODS
Flow cytometry, Southern blot, Northern blot and RT-PCR were used to examine genes and molecules related to drug resistance.


RESULTS
The drug-efflux of S-180R was nearly 100-fold as high as that of the parental cells. The ratio of half peak width to peak height was 0.23 as compared to 0.56 measured two years before when the S-180R cell line was initially established. The mdr-1 gene was significantly amplified and transcribed while the transcription of topoisomerase II alpha gene was decreased. However there was no increase in mRNA expression of the multidrug resistance associated protein(MRP).


CONCLUSIONS
Compared with the initially established S-180R, its resistance to doxorubicin is not only maintained but in fact has been increased since in vivo passage for 2 years. The major mechanism is amplification and over-expression of mdr-1 gene, but decreased topoisomerase II alpha also contributes. S-180R is an ideal experimental model for the study of doxorubicin resistance and its reversion.
School of Clinic Oncology, Beijing Medical University.
G
G
Zheng
T
T
Zhang
F
F
Han
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000818:Animals; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000494:pharmacology; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005784:Gene Amplification; D019450:Genes, MDR; D007527:Isoenzymes / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012510:Sarcoma 180 / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
D018528:ATP-Binding Cassette Transporters; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D004317:Doxorubicin; D007527:Isoenzymes; D027425:ATP-Binding Cassette, Sub-Family C Proteins