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Updated: Jun 27, 2026
Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence
Published on: November 2, 2014
[Proteasome inhibitors sensitize ovarian cancer cells to paclitaxel induced apoptosis]
Dan-Hui Weng1, Yan Li, Fan-Fei Kong
1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Objective:
To explore the sensitivity of ovarian cancer cell line SKOV3 to paclitaxel, proteasome inhibitors, bortezomib, and their combination.
Methods:
The methyl thiazolyl tetrazolium (MTT) assay was applied to examine the cell viability after treatment. The annexin V-propidium iodide apoptosis detection kit was used to determine the apoptosis rate of different groups. Western blot assay was used to evaluate the expression levels of phosphorylated protein kinase B (AKT) and glycogen synthase kinase-3 beta (GSK-3beta).
Results:
In MTT assay, the cell viability ratios of the combination group at serial time points from 12, 24, 36, 48 and 72 hours were (65.2 +/- 5.8)%, (58.3 +/- 14.4)%, (35.3 +/- 5.0)%, (19.2 +/- 1.5)%, and (11.4 +/- 2.5)%, which were significantly lower than those of the paclitaxel group (P < 0.05). After drug treatments, apoptosis rates of paclitaxel group, bortezomib group and the combination group were (14.7 +/- 0.5)%, (15.1 +/- 0.8)% and (20.5 +/- 0.7)% respectively. The rate of the combination group was significantly higher than that of non-treated group and paclitaxel group (P < 0.05). Western blot assay showed the changes in expression levels of phosphorylated AKT and GSK-3beta, which were decreased significantly after paclitaxel and bortezomib combination treatment [(3.2 +/- 0.8)%, (19.3 +/- 0.4)%; P < 0.05].
Conclusions:
The lethal effect of paclitaxel on tumor cells could be increased significantly by its combination with proteasome inhibitors, bortezomib. The AKT/GSK-3beta signaling pathway plays an important role in the molecular mechanism of the combination treatment.
Insights
Combining paclitaxel with proteasome inhibitors, bortezomib, significantly enhances its lethal effect on ovarian cancer cells. This combination therapy impacts the AKT/GSK-3beta signaling pathway, offering a potential new strategy for ovarian cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Ovarian cancer remains a leading cause of cancer-related deaths in women.
- Paclitaxel is a standard chemotherapeutic agent, but resistance can develop.
- Proteasome inhibitors, like bortezomib, offer an alternative therapeutic strategy.
Purpose of the Study:
- To investigate the combined efficacy of paclitaxel and bortezomib on the SKOV3 ovarian cancer cell line.
- To elucidate the role of the AKT/GSK-3beta signaling pathway in the response to this combination therapy.
Main Methods:
- Cell viability was assessed using the methyl thiazolyl tetrazolium (MTT) assay.
- Apoptosis rates were determined via annexin V-propidium iodide staining.
- Western blot analysis was employed to measure the expression of phosphorylated AKT and GSK-3beta.
Main Results:
- The combination of paclitaxel and bortezomib significantly reduced SKOV3 cell viability compared to paclitaxel alone.
- Combined treatment led to a significantly higher apoptosis rate than paclitaxel or bortezomib monotherapy.
- Expression of phosphorylated AKT and GSK-3beta was significantly decreased following combination treatment.
Conclusions:
- Paclitaxel's cytotoxic effect on ovarian cancer cells is potentiated by bortezomib.
- The AKT/GSK-3beta signaling pathway is implicated in the mechanism of action for this combination therapy.
- This combination strategy holds promise for overcoming paclitaxel resistance in ovarian cancer.
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