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.