Related Experiment Video
Updated: Apr 3, 2026
The Influence of Liver Resection on Intrahepatic Tumor Growth
Published on: April 9, 2016
Rapamycin and WYE-354 suppress human gallbladder cancer xenografts in mice
Helga Weber1, Pamela Leal1, Stefan Stein2
1Department of Pathology, Center of Genetic and Immunological Studies (CEGIN) and Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco, Chile.
Abstract:
Gallbladder cancer (GBC) is a highly malignant tumor characterized by a poor response to chemotherapy and radiotherapy. We evaluated the in vitro and in vivo antitumor efficacy of mTOR inhibitors, rapamycin and WYE-354. In vitro assays showed WYE-354 significantly reduced cell viability, migration and invasion and phospho-P70S6K expression in GBC cells. Mice harboring subcutaneous gallbladder tumors, treated with WYE-354 or rapamycin, exhibited a significant reduction in tumor mass. A short-term treatment with a higher dose of WYE-354 decreased the tumor size by 68.6% and 52.4%, in mice harboring G-415 or TGBC-2TKB tumors, respectively, compared to the control group. By contrast, treatment with a prolonged-low-dose regime of rapamycin almost abrogated tumor growth, exhibiting 92.7% and 97.1% reduction in tumor size, respectively, compared to control mice. These results were accompanied by a greater decrease in the phosphorylation status of P70S6K and a lower cell proliferation Ki67 index, compared to WYE-354 treated mice, suggesting a more effective mTOR pathway inhibition. These findings provide a proof of concept for the use of rapamycin or WYE-354 as potentially good candidates to be studied in clinical trials in GBC patients.
Insights
Rapamycin and WYE-354 show promise in treating gallbladder cancer (GBC). These mTOR inhibitors effectively reduced tumor growth and viability in preclinical models, suggesting potential for clinical trials.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Gallbladder cancer (GBC) is a highly malignant tumor with poor response to conventional therapies.
- The mammalian target of rapamycin (mTOR) pathway is implicated in various cancers, including GBC.
Purpose of the Study:
- To evaluate the in vitro and in vivo antitumor efficacy of mTOR inhibitors, rapamycin and WYE-354, in gallbladder cancer models.
- To assess the impact of these inhibitors on cell viability, migration, invasion, and key signaling pathways.
Main Methods:
- In vitro assays were performed on GBC cell lines to assess viability, migration, and invasion.
- In vivo studies involved treating mice with subcutaneous gallbladder tumors with WYE-354 or rapamycin.
- Changes in tumor mass, cell proliferation (Ki67 index), and mTOR pathway activity (phospho-P70S6K) were measured.
Main Results:
- WYE-354 significantly reduced GBC cell viability, migration, invasion, and phospho-P70S6K expression in vitro.
- Both WYE-354 and rapamycin significantly reduced tumor mass in vivo.
- Prolonged low-dose rapamycin demonstrated superior tumor growth inhibition (up to 97.1%) compared to WYE-354, with greater reduction in phospho-P70S6K and Ki67 index.
Conclusions:
- Rapamycin and WYE-354 exhibit significant antitumor activity against gallbladder cancer in preclinical models.
- Rapamycin, particularly with a prolonged low-dose regimen, showed enhanced efficacy in inhibiting the mTOR pathway and tumor growth.
- These findings support the further investigation of rapamycin and WYE-354 in clinical trials for GBC patients.
