Abstract
BackgroundCancer stem cells (CSCs) are thought to be capable of surviving conventional chemotherapeutic treatments because the cells have more resistant to anticancer drugs than common cancer cells. Most in vitro studies in experimental cancer cells have been done in a two-dimensional (2D) monocultures, while accumulating evidence suggests that cancer cells behave differently when they are grown within a three-dimensional (3D) culture system.ResultsThe CD44+CD117+cells isolated from human epithelial ovarian cancer SKOV-3 cell line using magnetic-activated cell sorting were found to grow faster than the SKOV-3 cells in the 3D culture and in the nude mice. Anticancer drugs 5FU, docetaxel, cisplatin, and carboplatin were seen to inhibit growth of the CD44+CD117+ cells by 50% in the 2D culture with IC50 concentration, whereas, in the 3D culture, the four drugs inhibited the cell growth by only 34.4%, 40.8%, 34.8% and 21.9% at 3D one, respectively. Effect of paclitaxel on the CD44+CD117+cell viability indicated that fewer cells underwent apoptosis in 3D culture than that in 2D one. In addition, anticancer drugs markedly increased the expression of ABCG2 and ABCB1 of CD44+CD117+cells in 3D culture.ConclusionOur assay demonstrated that human epithelial ovarian cancer CD44+CD117+cells possessed the properties of CSCs that exhibited more chemoresistance in the 3D culture than that of in 2D one. The 3D culture provides a realistic model for study of the CSC response to anticancer drugs.
Highlights
Cancer stem cells (CSCs) are thought to be capable of surviving conventional chemotherapeutic treatments because the cells have more resistant to anticancer drugs than common cancer cells
Morphologic characteristics and phenotype identification of CD44+CD117+cells First, to avoid the differentiation of epithelial ovarian cancer (EOC) CD44+CD117+cells in the common cell medium, the CD44+CD117+cells isolated from the SKOV-3 cell line by Magnetic associated cell sorting (MACS) were cultured in a stem cell culture medium
We firstly demonstrated that the CD44+CD117+cells that were isolated from the SKOV-3 ovarian cell line and were identified by immunofluorescence microscope and the Flow cytometer (FCM) (Figure 1) possessed the CSC properties
Summary
Cancer stem cells (CSCs) are thought to be capable of surviving conventional chemotherapeutic treatments because the cells have more resistant to anticancer drugs than common cancer cells. Conclusion: Our assay demonstrated that human epithelial ovarian cancer CD44+CD117+cells possessed the properties of CSCs that exhibited more chemoresistance in the 3D culture than that of in 2D one. Ovarian cancer is the number one leading cause of death among gynecologic malignancies. This is due mainly to the prevalence of this undetected metastatic disease as over 90% of malignant tumors are epithelial ovarian cancer (EOC). It is believed that the cytotoxic effects of chemotherapy kill most cells in a tumor but CSCs are leave behind; this might be an important mechanism of the observed resistance to the treatment. CSCs are even more chemoresistant and more aggressive than their original tumor cells [7,8,9]
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