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The effect of salinomycin on ovarian cancer stem-like cells
Hyewon Chung1, Yu-Hwan Kim1, Myoung Kwon1
1Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Korea.
Objective:
The identification of cancer stem-like cells is a recent development in ovarian cancer. Compared to other cancer cells, cancer stem-like cells present more chemo-resistance and more aggressive characteristics. They play an important role in the recurrence and drug resistance of cancer. Therefore, the target therapy of cancer stem-like cell may become a promising and effective approach for ovarian cancer treatment. It may also help to provide novel diagnostic and therapeutic strategies.
Methods:
The OVCAR3 cell line was cultured under serum-free conditions to produce floating spheres. The CD44(+)CD117(+) cell line was isolated from the human ovarian cancer cell line OVCAR3 by using immune magnetic-activated cell sorting system. The expression of stemness genes such as OCT3/4, NANOG and SOX2 mRNA were determined by reverse transcription polymerase chain reaction. OVCAR3 parental and OVCAR3 CD44(+)CD117(+) cells were grown in different doses of paclitaxel and salinomycin to evaluate the effect of salinomycin. And growth inhibition of OVCAR3 CD44(+)CD117(+) cells by paclitaxel combined with salinomycin was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay.
Results:
Tumor spheroids generated from the OVCAR3 cell line are shown to have highly enriched CD44 and CD117 expression. Treatment with a combination of paclitaxel and salinomycin demonstrated growth inhibition of OVCAR3 CD44(+)CD117(+) cells.
Conclusion:
The present study is a detailed investigation on the expression of CD44 and CD117 in cancer stem cells and evaluates their specific tumorigenic characteristics in ovarian cancer. This study also demonstrates significant growth inhibition of cancer stem-like cells by paclitaxel combined with salinomycin. Identification of these cancer stem-like cell markers and growth inhibition effect of salinomycin may be the next step to the development of novel target therapy in ovarian cancer.
Insights
Cancer stem-like cells in ovarian cancer exhibit chemo-resistance and drive recurrence. Combining paclitaxel and salinomycin effectively inhibits the growth of these aggressive ovarian cancer stem cells.
Area of Science:
- Oncology
- Cancer Stem Cell Biology
Background:
- Cancer stem-like cells (CSCs) are implicated in ovarian cancer's chemo-resistance and recurrence.
- Targeting CSCs offers a promising strategy for novel ovarian cancer diagnostics and therapeutics.
Purpose of the Study:
- To investigate the expression of CD44 and CD117 markers in ovarian cancer stem-like cells.
- To evaluate the therapeutic potential of combining paclitaxel and salinomycin against these cells.
Main Methods:
- Isolation of CD44(+)CD117(+) ovarian cancer stem-like cells from the OVCAR3 cell line using magnetic-activated cell sorting.
- Assessment of stemness gene expression (OCT3/4, NANOG, SOX2) via reverse transcription polymerase chain reaction.
- Evaluation of growth inhibition using MTT assay after treatment with paclitaxel and salinomycin.
Main Results:
- Ovarian cancer spheroids showed enriched expression of CD44 and CD117.
- Combined treatment with paclitaxel and salinomycin significantly inhibited the growth of OVCAR3 CD44(+)CD117(+) cells.
Conclusions:
- CD44 and CD117 are key markers for identifying ovarian cancer stem-like cells.
- The combination of paclitaxel and salinomycin demonstrates significant efficacy in inhibiting CSC growth, paving the way for new targeted therapies.
