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Development of doxorubicin resistant rat prostate cancer cell lines
T S Replogle-Schwab1, E D Schwab, K J Pienta
1University of Michigan Comprehensive Cancer Center, Ann Arbor 48109-0932, USA.
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.
Materials And 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.