TY  - JOUR
A1  - Weber, Helga
A1  - Leal-Rojas, Pamela
A1  - Stein, Stefan
A1  - Kunkel, Hana
A1  - García, Patricia
A1  - Bizama, Carolina
A1  - Espinoza, Jaime A.
A1  - Riquelme, Ismael
A1  - Nervi, Bruno
A1  - Araya, Juan C.
A1  - Grez, Manuel
A1  - Roa, Juan Carlos
T1  - Rapamycin and WYE-354 suppress human gallbladder cancer xenografts in mice
T2  - Oncotarget
N2  - 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.
KW  - gallbladder cancer
KW  - mTOR inhibitors
KW  - gallbladder cancer xenografts
KW  - rapamycin
KW  - WYE-354
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/41287
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-412871
SN  - 1949-2553
N1  - Licensed under a Creative Commons Attribution 3.0 License.
VL  - 6
IS  - 31
SP  - 31877
EP  - 31888
PB  - Impact Journals LLC
CY  - [s. l.]
ER  -