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Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines
Published on: September 10, 2014
Silibinin restores paclitaxel sensitivity to paclitaxel-resistant human ovarian carcinoma cells
Liguang Zhou1, Peishu Liu, Bo Chen
1Departments of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 250012 Jinan, ROC.
Background:
Drug resistance and tumor metastasis are the main causes of treatment failure and mortality in cancer patients. Silibinin, a naturally occurring flavanone, has been shown to be a potent sensitizer for apoptosis induced by a variety of anticancer drugs. In this study, whether silibinin could overcome chemoresistance and reduce the invasiveness of A2780/taxol cells was investigated.
Materials And Methods:
A2780 and A2780/taxol cells were treated with silibinin alone and in combination with paclitaxel. Cell viability was determined by MTT assay while apoptosis and cell cycle progression were assessed by flow cytometric analysis. Matrigel invasion assays assessed the invasive activity. Protein and mRNA levels influenced by the treatment were studied by Western blots and quantitative real-time PCR.
Results:
Silibinin enhanced the sensitivity of A2780/taxol cells to paclitaxel, increased paclitaxel-induced apoptosis and G2/M arrest consistent with the down-regulation of survivin and P-glycoproteins. A2780/taxol cells demonstrated a two-fold increase in invasiveness ability compared to A2780 cells, whereas the invasive potential was reduced dramatically by silibinin.
Conclusion:
These results suggest silibinin in combination with paclitaxel may be a beneficial chemotherapeutic strategy, especially in patients with tumors refractory to paclitaxel alone.
Insights
Silibinin enhances paclitaxel effectiveness against drug-resistant ovarian cancer cells by increasing apoptosis and reducing metastasis. This combination therapy shows promise for treating paclitaxel-refractory tumors.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Drug resistance and metastasis are primary causes of cancer treatment failure and mortality.
- Silibinin, a natural flavanone, sensitizes cancer cells to apoptosis induced by various anticancer drugs.
- This study investigates silibinin's potential to overcome chemoresistance and reduce invasiveness in paclitaxel-resistant ovarian cancer cells (A2780/taxol).
Purpose of the Study:
- To evaluate silibinin's efficacy in overcoming paclitaxel resistance in A2780/taxol cells.
- To assess silibinin's impact on paclitaxel-induced apoptosis, cell cycle arrest, and invasiveness.
- To explore the molecular mechanisms underlying silibinin's effects on chemoresistance and metastasis.
Main Methods:
- Cell viability was assessed using MTT assays.
- Apoptosis and cell cycle progression were analyzed via flow cytometry.
- Invasiveness was measured using Matrigel invasion assays, with protein and mRNA levels analyzed by Western blot and qPCR.
Main Results:
- Silibinin significantly enhanced A2780/taxol cell sensitivity to paclitaxel, increasing apoptosis and G2/M arrest.
- These effects correlated with the down-regulation of survivin and P-glycoproteins.
- Silibinin dramatically reduced the invasive potential of A2780/taxol cells, which exhibit higher invasiveness than A2780 cells.
Conclusions:
- Silibinin combined with paclitaxel presents a potentially beneficial chemotherapeutic strategy.
- This combination is particularly relevant for patients with tumors resistant to paclitaxel monotherapy.
- Silibinin demonstrates potential in combating both chemoresistance and tumor metastasis.
