Development of doxorubicin resistant rat prostate cancer cell lines.
BACKGROUND
One possible mechanism of chemotherapeutic resistance in patients with metastatic prostate cancer is the overexpression of P-glycoprotein. Additional tumor models are necessary to study this phenomenon.


METHODS
Doxorubicin resistant rat prostate cancer cell lines were developed by increasing doxorubicin levels in cell culture.


RESULTS
The MDR lines (AT3B-1, AT3B-2, MLLB-1, and MLLB-2) were more resistant to vinblastine compared to controls. When P-glycoprotein was blocked, the AT3 MDR lines demonstrated efflux activity. Injection of AT3 MDR lines into rats followed by doxorubicin treatment produced larger tumors compared to the parental controls.


CONCLUSIONS
MDR rat prostate cancer cells were developed. AT3B-1 and AT3B-2 cell lines have drug efflux pump ability, whereas the MLLB-1 and MLLB-2 may not, suggesting alternative key mechanisms other than P-glycoprotein overexpression. These new cell lines are being used to study chemotherapy resistance in prostate cancer.
Replogle-Schwab
T S
TS
University of Michigan Comprehensive Cancer Center, Ann Arbor 48109-0932, USA.
Schwab
E D
ED
Pienta
K J
KJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000633:toxicity*; D018432:Drug Resistance, Multiple; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D051381:Rats; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000493:pharmacokinetics / Q000633:toxicity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014747:Vinblastine; D004317:Doxorubicin