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Published on: February 6, 2015
Transcriptome analysis reveals the anticancer effects of fenbendazole on ovarian cancer: an in vitro and in vivo
Xin Wang1, Wenda Tian1, Ning Wang2
1Department of Gynecology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, 650118, Yunnan, P. R. China.
Abstract:
New treatment strategies for ovarian cancer, which is the deadliest female reproductive tract malignancy, are urgently needed. Here, we investigated the anticancer effects of fenbendazole (FBZ), a benzimidazole compound, on the regulation of apoptosis and mitotic catastrophe in A2780 and SKOV3 human epithelial ovarian cancer cells. Functional experiments, including Cell Counting Kit 8 (CCK-8), colony formation, and flow cytometry assays, were conducted to explore the effects of FBZ on the malignant biological behavior of A2780 and SKOV3 cells. RNA sequencing and western blotting were utilized to elucidate the underlying mechanisms by which FBZ affects cell apoptosis. We found that FBZ inhibited the proliferation and promoted the apoptosis of ovarian cancer cells in a dose-dependent manner. Furthermore, we reported the transcriptome profiling of FBZ-treated SKOV3 ovarian cancer cells. In all, 1747 differentially expressed genes (DEGs) were identified, including 944 downregulated and 803 upregulated genes. KEGG enrichment and Reactome enrichment analyses revealed that the DEGs were associated mainly with mitosis- and cell cycle-related pathways. Additionally, we found that FBZ may promote apoptosis via mitotic catastrophe. Finally, oral administration of FBZ inhibited tumor growth in a mouse model of xenograft ovarian cancer. Overall, these findings suggest that FBZ has therapeutic potential for the treatment of ovarian cancer.
Insights
Fenbendazole (FBZ) shows promise as an ovarian cancer treatment by inhibiting cancer cell growth and promoting apoptosis. This study reveals FBZ
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Ovarian cancer remains a leading cause of cancer-related mortality in women.
- Novel therapeutic strategies are crucial for improving patient outcomes.
- Benzimidazole compounds, like fenbendazole (FBZ), are being explored for anticancer properties.
Purpose of the Study:
- To investigate the anticancer effects of fenbendazole (FBZ) on human epithelial ovarian cancer cells.
- To elucidate the mechanisms of FBZ-induced apoptosis and mitotic catastrophe.
- To evaluate the in vivo efficacy of FBZ in a xenograft ovarian cancer model.
Main Methods:
- Cell proliferation assays (CCK-8, colony formation) and flow cytometry were used to assess FBZ effects on A2780 and SKOV3 cells.
- RNA sequencing and western blotting were employed to identify molecular mechanisms.
- Tumor growth inhibition was evaluated in a mouse xenograft model.
Main Results:
- FBZ significantly inhibited ovarian cancer cell proliferation and induced apoptosis in a dose-dependent manner.
- Transcriptome profiling revealed FBZ-regulated genes primarily involved in mitosis and cell cycle pathways.
- FBZ treatment led to mitotic catastrophe and apoptosis, and suppressed tumor growth in vivo.
Conclusions:
- Fenbendazole (FBZ) demonstrates significant anticancer activity against ovarian cancer cells.
- FBZ exerts its effects by disrupting cell cycle progression and inducing mitotic catastrophe.
- FBZ holds therapeutic potential for treating ovarian cancer.
