Isolation and characterization of multidrug-resistant side population cells in prostate carcinoma
Purpose: To isolate and characterize cancer stem-like side population (SP) cells from prostate cancer tissues using Hoechst 33342 dye exclusion.
Methods: The presence of SP cells was analyzed in tumor samples by fluorescence activated cell sorting. The cell survival rate and ability for cell self-renewal using the sphere formation assay were evaluated after treatment with multiple drugs.
Results: SP cells in the prostate cancer samples constituted 2.8 %, but fell to 0.6 % after treatment with verapamil. The SP cells showed high resistance to drugs such as 5-fluorouracil, cisplatin, paclitaxel (2 μmol/L) and oxaliplatin. The survival rate of SP cells after treatment with these drugs was significantly higher (p < 0.01) than that of non-SP cells. Furthermore, the number of spheres generated in serumfree medium was significantly higher in prostate cancer SP cells than in non-SP cells.
Conclusion: The presence of SP cells is responsible for prostate treatment failure and tumor recurrence. Therefore, isolation and characterization of SP cells may provide new insights into the development of novel therapeutic agents targeting cancer stem cells for complete eradication of the tumor.
Keywords: Side population cells, ABC transporters, Cancer stem cells, Chemotherapy, Prostate treatment failure, Tumor recurrence, Drug resistance