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Journal articles
Multicellular tumor spheroid model to evaluate spatio-temporal dynamics effect of chemotherapeutics: application to the gemcitabine/CHK1 inhibitor combination in pancreatic cancer.
Abstract : UNLABELLED: ABSTRACT: BACKGROUND: The multicellular tumor spheroid (MCTS) is an in vitro model associating malignant-cell microenvironment and 3D organization as currently observed in avascular tumors. METHODS: In order to evaluate the relevance of this model for pre-clinical studies of drug combinations, we analyzed the effect of gemcitabine alone and in combination with the CHIR-124 CHK1 inhibitor in a Capan-2 pancreatic cell MCTS model. RESULTS: Compared to monolayer cultures, Capan-2 MCTS exhibited resistance to gemcitabine cytotoxic effect. This resistance was amplified in EGF-deprived quiescent spheroid suggesting that quiescent cells are playing a role in gemcitabine multicellular resistance. After a prolonged incubation with gemcitabine, DNA damages and massive apoptosis were observed throughout the spheroid while cell cycle arrest was restricted to the outer cell layer, indicating that gemcitabine-induced apoptosis is directly correlated to DNA damages. The combination of gemcitabine and CHIR-124 in this MCTS model, enhanced the sensitivity to the gemcitabine antiproliferative effect in correlation with an increase in DNA damage and apoptosis. CONCLUSIONS: These results demonstrate that our pancreatic MCTS model, suitable for both screening and imaging analysis, is a valuable advanced tool for evaluating the spatio-temporal effect of drugs and drug combinations in a chemoresistant and microenvironment-depending tumor model.
Cited literature [35 references]
https://www.hal.inserm.fr/inserm-00670715
Contributor : Ed. Bmc Connect in order to contact the contributor
Submitted on : Wednesday, February 15, 2012 - 9:05:12 PM
Last modification on : Wednesday, January 19, 2022 - 2:10:02 PM
Long-term archiving on: : Thursday, November 22, 2012 - 12:51:16 PM
Contributor : Ed. Bmc Connect in order to contact the contributor
Submitted on : Wednesday, February 15, 2012 - 9:05:12 PM
Last modification on : Wednesday, January 19, 2022 - 2:10:02 PM
Long-term archiving on: : Thursday, November 22, 2012 - 12:51:16 PM