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An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Oridonin Suppresses Bladder Cancer Growth and Metastasis by Inducing S-Phase Arrest and Apoptosis
Wenqiang Sun1, Yongchao Li1, Menglong Xu1
1The State Key Laboratory Incubation Base for Conservation and Utilization of Bio-Resource in the Tarim Basin of the Xinjiang Production and Construction Corps, Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Tarim University, Alar 843300, China.
Abstract:
Bladder cancer (BC) remains a major clinical challenge owing to limited therapeutic options and high recurrence rates. Oridonin (ORI), a natural diterpenoid derived from Rabdosia plants, exhibits promising anti-tumor activity, but its effects and mechanisms in BC remain poorly defined. We evaluated the anti-BC potential of ORI in vitro and in vivo using proliferation, migration, invasion, cell-cycle, and apoptosis assays, integrated transcriptomic and proteomic analyses, Western blotting, and a 5637 xenograft model. ORI dose- and time-dependently inhibited 5637 and T24 cell proliferation, induced S-phase arrest (from 23.37% to 42.12% in 5637 and from 31.87% to 50.28% in T24; p < 0.01), and reduced migration (from 53.39% to 13.77% and from 59.81% to 12.49%; p < 0.0001) and invasion (from 74.42% to 25.43% and from 67.03% to 30.12%; p < 0.001). Multi-omics analyses revealed widespread changes enriched in apoptosis- and cell-cycle-related pathways. Consistently, ORI promoted apoptosis and necrosis, up-regulating BAX, CASP3, BID, and CYCS and down-regulating BCL2, validating the omics findings. In vivo, ORI (20 mg/kg, daily gavage) significantly suppressed xenograft growth (p < 0.001) without obvious toxicity, indicating that ORI inhibits BC growth and metastasis by inducing S-phase arrest and apoptosis and is a promising candidate for BC therapy.
Insights
Oridonin (ORI), a natural compound, effectively inhibits bladder cancer (BC) growth and metastasis. ORI induces cell cycle arrest and apoptosis, showing promise as a novel BC therapeutic agent with minimal toxicity.
Area of Science:
- Oncology
- Pharmacology
- Natural Products Chemistry
Background:
- Bladder cancer (BC) presents significant therapeutic challenges due to limited treatment options and high recurrence rates.
- Oridonin (ORI), a natural diterpenoid from *Rabdosia* plants, shows potential anti-tumor effects, but its role in BC is not well understood.
Purpose of the Study:
- To investigate the anti-cancer effects and underlying mechanisms of Oridonin (ORI) in bladder cancer (BC) models.
- To evaluate ORI's efficacy and safety in vitro and in vivo for potential BC therapy.
Main Methods:
- Utilized in vitro assays (proliferation, migration, invasion, cell-cycle, apoptosis) and in vivo xenograft models.
- Integrated transcriptomic and proteomic analyses, Western blotting to elucidate molecular mechanisms.
- Oridonin (ORI) treatment effects were assessed in 5637 and T24 bladder cancer cell lines and a 5637 xenograft mouse model.
Main Results:
- Oridonin (ORI) dose- and time-dependently inhibited bladder cancer cell proliferation, migration, and invasion.
- ORI induced significant S-phase arrest and promoted apoptosis and necrosis, evidenced by altered expression of apoptosis-related proteins (BAX, CASP3, BID, CYCS, BCL2).
- In vivo, Oridonin (ORI) significantly suppressed tumor growth in a 5637 xenograft model without apparent toxicity.
Conclusions:
- Oridonin (ORI) demonstrates significant anti-bladder cancer activity by inducing S-phase arrest and apoptosis.
- ORI effectively inhibits BC growth and metastasis, suggesting its potential as a promising therapeutic candidate for bladder cancer.
- The findings support further investigation of Oridonin (ORI) for clinical application in bladder cancer treatment.

