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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
[Inhibitory effect of BEZ235 on human prostate carcinoma in vitro]
Guojun Hou1, Huilin Que2, Jie Sun2
1Department of Urinary Surgery, Affiliated Hospital, Yanbian University, Yanji Jilin 133000, China.
Objective:
To determine effects of BEZ235, an inhibitor of phosphoionsitol-3-kinase (PI3K)/mTOR, on the cell proliferation and migration in human prostate carcinoma lines including RWPE-1, PC3, and DU145 cells. Methods: Viability of RWPE-1, PC3, and DU145 cells was detected by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, while cell migration was analyzed by wound healing assay. Western blot and immunofluorescence were used to examine the changes of relevant protein expression. Results: The proliferation of PC3 and DU145 cells was effectively inhibited by BEZ235 (P<0.01), whereas RWPE-1 was not obviously inhibited. Invasion and migration of PC3 and DU145 cells were attenuated by BEZ235 via EMT pathway. Conclusion: The PI3K/mTOR dual inhibitor BEZ235 shows substantial anti-tumor activity in human prostate carcinoma lines of PC3 and DU145 cells, which may be involved in the EMT pathway.
Insights
The PI3K/mTOR inhibitor BEZ235 significantly reduced prostate cancer cell proliferation and migration in PC3 and DU145 lines. This dual inhibitor demonstrated anti-tumor effects, potentially through the epithelial-mesenchymal transition (EMT) pathway.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Prostate carcinoma is a significant health concern with ongoing research into targeted therapies.
- Phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathways are frequently dysregulated in cancer.
- Identifying novel inhibitors targeting these pathways is crucial for effective prostate cancer treatment.
Purpose of the Study:
- To investigate the anti-proliferative and anti-migratory effects of BEZ235, a dual PI3K/mTOR inhibitor.
- To assess the impact of BEZ235 on human prostate carcinoma cell lines (RWPE-1, PC3, DU145).
- To explore the underlying molecular mechanisms, including the epithelial-mesenchymal transition (EMT) pathway.
Main Methods:
- Cell viability was assessed using the MTT assay.
- Cell migration was analyzed via the wound healing assay.
- Protein expression changes were examined using Western blot and immunofluorescence.
Main Results:
- BEZ235 significantly inhibited the proliferation of PC3 and DU145 prostate cancer cells (P<0.01).
- RWPE-1 cells showed no significant inhibition in proliferation.
- BEZ235 attenuated the invasion and migration of PC3 and DU145 cells, suggesting involvement of the EMT pathway.
Conclusions:
- BEZ235 exhibits substantial anti-tumor activity against human prostate carcinoma cell lines PC3 and DU145.
- The anti-cancer effects of BEZ235 may be mediated through modulation of the EMT pathway.
- BEZ235 represents a potential therapeutic agent for specific subtypes of prostate cancer.
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