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Updated: Dec 25, 2025
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
CD133 suppression increases the sensitivity of prostate cancer cells to paclitaxel
Marjan Aghajani1, Ahad Mokhtarzadeh1, Leili Aghebati-Maleki1
1Immunology Research Center, Tabriz University of Medical Sciences, Daneshghah Ave, Tabriz, Iran.
Abstract:
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.
Insights
Targeting CD133 with siRNA and paclitaxel overcomes chemoresistance in prostate cancer (PC) by reducing cancer stem cell (CSC) properties. This combination therapy enhances apoptosis and suppresses migration, offering a promising strategy for PC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Cancer stem cells (CSCs) drive therapy resistance and recurrence in various cancers, including prostate cancer (PC).
- CD133 is a marker associated with CSC properties, tumorigenicity, and drug resistance, but its precise role in PC remains unclear.
- Conventional therapies often face resistance, necessitating novel therapeutic strategies targeting CSCs.
Purpose of the Study:
- To investigate the molecular mechanism of CD133-siRNA and paclitaxel in reducing chemoresistance in PC cells.
- To evaluate the combined effect of CD133 silencing and paclitaxel on CSC properties, proliferation, migration, invasion, and apoptosis.
- To elucidate the impact of CD133 silencing on the AKT/mTOR/c-myc signaling pathway and pro-metastatic gene expression.
Main Methods:
- Utilized MTT, wound healing, spheroid, and colony formation assays to assess cell viability, migration, and CSC properties.
- Employed DAPI staining and flow cytometry to analyze apoptosis and cell cycle progression.
- Applied quantitative real-time PCR (qRT-PCR) and Western blot to measure CD133 expression and its effects on signaling pathways and gene expression.
Main Results:
- CD133-siRNA significantly reduced CD133 expression in LNCaP cells.
- Combined CD133-siRNA and paclitaxel treatment suppressed cell proliferation, migration, invasion, and pro-metastatic gene expression.
- The combination therapy synergistically enhanced paclitaxel-induced apoptosis and improved chemosensitivity compared to monotherapy.
Conclusions:
- CD133 silencing, in combination with paclitaxel, effectively suppresses key hallmarks of prostate cancer progression.
- This synergistic approach enhances chemosensitivity, suggesting CD133 silencing as a potent therapeutic strategy for overcoming chemoresistance in PC.
- Targeting CD133 holds significant promise for developing novel, effective therapies for prostate cancer.
