CD133 suppression increases the sensitivity of prostate cancer cells to paclitaxel.

Mol Biol Rep 2020 May 3;47(5):3691-3703. Epub 2020 Apr 3.

Immunology Research Center, Tabriz University of Medical Sciences, Daneshghah Ave, Tabriz, Iran.

One of the major barriers in cancer therapy is the resistance to conventional therapies and cancer stem cells (CSCs) are among the main causes of this problem. CD133 as a CSC marker displays stem cell-like properties, tumorigenic capacity, and drug resistance in various cancers. However, the molecular mechanism behind CD133 function in prostate cancer (PC) still remains unclear. This research aimed to illustrate the probabilistic mechanism of CD133-siRNA and paclitaxel in the reduction of chemoresistance in PC cells. To measure the cell viability, migratory capacity, CSCs properties, invasive potential, apoptosis and cell cycle progression of the cells, the MTT, wound healing, spheroid assay, colony formation assay, DAPI staining and flow cytometry assays were applied in the LNCaP cell line, respectively. Also, quantitative real-time PCR (qRT-PCR) and western blot method were used for measuring the expression of CD133 and the effects of CD133 silencing on the AKT/mTOR/c-myc axis and pro-metastatic genes expression. We showed that the CD133-siRNA considerably decreased the CD133 expression. Moreover, CD133-siRNA and paclitaxel treatment significantly decreased cell proliferation and also inhibited the ability of cell migration and invasion and reduced pro-metastatic genes expression. Additionally, we found that the simultaneous use of CD133-siRNA and paclitaxel increased the paclitaxel-induced apoptosis. Our results confirmed that CD133 silencing combined with paclitaxel synergistically could suppress cell migration, invasion, and proliferation and enhance the chemosensitivity compared with mono treatment. Therefore, CD133 silencing therapy could be viewed as a promising and efficient strategy in PC targeted therapies.

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http://dx.doi.org/10.1007/s11033-020-05411-9DOI Listing
May 2020
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