Abstract
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
Highlights
Prostate cancer is the most common cancer among males and one of the leading causes of death worldwide [1]
As shown in the dot plot generated from the fluorescence activated cell sorting (FACS) data (Figure 1), the proportion of side population (SP) cells observed was approximately 2.8 %
To examine the chemoresistant phenotype and self-renewing capacity of the Cancer stem cells (CSCs), the sorted SP and non-SP cells were subjected to drug resistance and sphere formation assays
Summary
Prostate cancer is the most common cancer among males and one of the leading causes of death worldwide [1]. Prostate cancer cells are highly drugresistant, which results in treatment failure and a high mortality rate. The major implications of drug resistance in tumor biology are often associated with chemotherapy failure, recurrence of the tumor and metastasis. Cancer stem cells (CSCs) have been identified as a small subset of cells within a tumor population. Several studies have demonstrated that the presence of CSCs is responsible for chemotherapy resistance and treatment failure. The biological characteristics of CSCs, such as self-renewal and a high proliferation rate, are similar to those of normal stem cells, which could have a detrimental effect on cancer treatment [24]. Understanding the mechanism of CSCs in tumor relapse, as well as improved cancer treatments that target and kill CSCs, are urgently needed in the current field of cancer treatment
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