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Updated: Aug 29, 2026

3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
The phosphatidylinositol-3 kinase pathway regulates bladder cancer cell invasion
Objectives:
To investigate the role of the phosphatidylinositol (PI)-3 kinase pathway in the invasion of bladder cancer cell lines, and to assess the activation of this pathway in primary human bladder tumours.
Materials And Methods:
Human bladder cancer cells were treated with pathway specific inhibitors or were transfected with PI-3 kinase pathway components. The invasion of cultured bladder cancer cells was analysed by an invasion assay. Bladder cancer cells lines and primary human bladder tumours were analysed for pathway activation by western blotting.
Results:
A specific inhibitor of PI-3 kinase enzyme activity, Ly294002, potently suppressed the invasive properties of three highly invasive bladder tumour cell lines. Restoration of the PTEN gene to invasive UM-UC-3 bladder tumour cells or expression of a dominant-negative version of the PI-3 kinase target, Akt, also potently inhibited invasion, indicating a central role for the PI-3 kinase/Akt pathway in this process. In addition, 55% of primary tumours from patients with bladder cancer had markedly high levels of phosphorylated Akt.
Conclusion:
Pharmacological or biochemical inhibition of the PI-3 kinase pathway drastically reduced the invasive capacity of bladder cancer cell lines; over half of primary human bladder tumours had high Akt phosphorylation, suggesting that the aberrant activation of this pathway may contribute to the invasion of a significant subset of bladder cancers.
Insights
The phosphatidylinositol 3-kinase (PI-3K) pathway is crucial for bladder cancer cell invasion. Inhibiting this pathway significantly reduced cancer cell invasiveness, and over half of primary bladder tumors showed high pathway activation.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The phosphatidylinositol 3-kinase (PI-3K) pathway plays a critical role in cellular processes.
- Aberrant activation of the PI-3K pathway is implicated in various cancers, including bladder cancer.
Purpose of the Study:
- To investigate the role of the PI-3K pathway in bladder cancer cell invasion.
- To assess PI-3K pathway activation in primary human bladder tumors.
Main Methods:
- Bladder cancer cell lines were treated with PI-3K pathway inhibitors or transfected with pathway components.
- Invasion assays were used to analyze cell invasiveness.
- Western blotting was employed to detect pathway activation in cell lines and primary tumors.
Main Results:
- The PI-3K inhibitor Ly294002 significantly suppressed the invasion of highly invasive bladder cancer cell lines.
- Restoring PTEN or expressing dominant-negative Akt inhibited invasion, confirming the PI-3K/Akt pathway's central role.
- 55% of primary bladder tumors exhibited high levels of phosphorylated Akt, indicating pathway activation.
Conclusions:
- Inhibiting the PI-3K pathway drastically reduced bladder cancer cell invasiveness.
- High Akt phosphorylation in over half of primary bladder tumors suggests aberrant PI-3K pathway activation contributes to invasion in a significant subset of bladder cancers.
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