Inhibition of Autophagy Strengthens Celastrol-Induced Apoptosis in Human Pancreatic Cancer In Vitro and In Vivo Models

Author(s): X. Zhao, S. Gao, H. Ren, H. Huang, W. Ji, J. Hao

Journal Name: Current Molecular Medicine

Volume 14 , Issue 4 , 2014

Become EABM
Become Reviewer
Call for Editor


Objectives: Celastrol, a quinone methide triterpenoid, could induce apoptosis in pancreatic cancer cells. The purpose of this study is to determine whether there is protective autophagy after celastrol treatment in pancreatic cancer cells and the synergistic effects of celastrol and 3-MA in vitro and in vivo.

Methods: The cells viability was measured using MTT assays. Degree of apoptosis and amount of autophagic vacuoles were measured by flow cytometry. Immunofluorescence was adapted to monitor the localization of autophagic protein LC3-II. Expression of LC3-II, cleaved caspase-3, Bax and bcl-2 was detected by immunoblot. Autophagosomes were observed by electron microscopy. The synergistic effect of celastrol and 3- MA in vivo was studied in the MiaPaCa-2 xenograft tumor model.

Results: Celastrol increased the level of autophagy in pancreatic cancer cells. Furthermore in vitro, when inhibiting the autophagy with 3-MA, the level of celastrol-induced apoptosis elevated; after upgrading autophagy by starvation, the level of celastrol-induced apoptosis descended. 3-MA enhanced celastrol-induced apoptosis and inhibitory effect on tumor growth in vivo.

Conclusions: In pancreatic cancer, celastrol treatment increased the level of autophagy to protect cancer cells against apoptosis. Autophagy inhibitor 3-MA could improve the therapeutic effect of celastrol in vitro and in vivo.

Keywords: 3-methyladenine, apoptosis, autophagy, celastrol, pancreatic cancer, PTEN.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2014
Published on: 05 May, 2014
Page: [555 - 563]
Pages: 9
DOI: 10.2174/1566524014666140414211223
Price: $65

Article Metrics

PDF: 46