Curcumin Inhibits Bladder Cancer by Inhibiting Invasion via AKT/MMP14 Pathway
Kai Wang1, Wen Xiao2,3, Qi Zeng4
1Department of Pharmacy, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), 410006 Changsha, Hunan, China.
Background:
Bladder cancer is a malignant tumor of the urinary and reproductive tract that seriously threatens human health. It is urgent to develop new drugs for bladder cancer. This study aims to explore whether curcumin could inhibit bladder cancer and the potential mechanism.
Methods:
Firstly, network pharmacology was applied to explore the potential target of curcumin in bladder cancer. Among the potential target of curcumin on bladder cancer, the role of matrix metalloproteinase-14 (MMP14) was further explored by bioinformatic analysis and the expression of MMP14 was confirmed by immunohistochemistry staining. The effect of curcumin on bladder cancer was then studied using the cell counting kit-8 (CCK-8) assay, clone formation assay, apoptosis assay, and Transwell assay. Finally, AKT, MMP14, E-cadherin and N-cadherin were analyzed by Western blot assay to confirm whether curcumin could inhibit bladder cancer by inhibiting invasion via AKT/MMP14 pathway.
Results:
In the present study, we found that the target of curcumin for bladder cancer includes signal transducer and activator of transcription 3 (STAT3), AKT, cyclin A2 (CCNA2), epidermal growth factor receptor (EGFR), E1A binding protein p300 (EP300) and MMP14. MMP14 was highly expressed in bladder cancer than in normal tissues and was associated with a worse prognosis (p < 0.05). Curcumin could inhibit the proliferation and migration of bladder cancer cells (p < 0.05), while promoting cell apoptosis by inhibiting the AKT/MMP14 pathway (p < 0.05).
Conclusion:
Curcumin could inhibit bladder cancer by inhibiting invasion through the AKT/MMP14 pathway.
Insights
Curcumin shows potential in treating bladder cancer by inhibiting cell invasion. This study reveals curcumin suppresses proliferation and migration while promoting apoptosis via the AKT/MMP14 pathway.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Bladder cancer poses a significant health threat, necessitating novel therapeutic agents.
- Current treatment options for bladder cancer require enhancement.
- Exploring natural compounds like curcumin offers a promising avenue for drug development.
Purpose of the Study:
- To investigate the inhibitory effects of curcumin on bladder cancer.
- To elucidate the underlying molecular mechanisms of curcumin's action in bladder cancer.
- To identify key molecular targets of curcumin in bladder cancer treatment.
Main Methods:
- Network pharmacology identified potential curcumin targets in bladder cancer.
- Bioinformatic analysis and immunohistochemistry validated matrix metalloproteinase-14 (MMP14) as a key target.
- In vitro assays (CCK-8, clone formation, apoptosis, Transwell) assessed curcumin's effects on bladder cancer cells.
- Western blot analysis examined the AKT/MMP14 signaling pathway.
Main Results:
- Curcumin targets include STAT3, AKT, CCNA2, EGFR, EP300, and MMP14.
- MMP14 expression is elevated in bladder cancer tissues and correlates with poor prognosis.
- Curcumin significantly inhibited bladder cancer cell proliferation and migration.
- Curcumin treatment promoted apoptosis in bladder cancer cells.
Conclusions:
- Curcumin effectively inhibits bladder cancer progression.
- The AKT/MMP14 signaling pathway is a critical mediator of curcumin's anti-cancer effects.
- Curcumin demonstrates therapeutic potential for bladder cancer by targeting invasion via the AKT/MMP14 pathway.
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