Synergism of CPT-11 and Apo2L/TRAIL against two differentially sensitive human colon tumor xenografts.

Oncology
Kenji SugamuraBonnie L Hylander

Abstract

The ability to sustain and grow portions of human tumors as xenografts in SCID mice provides a valuable preclinical opportunity to test the response of human tumors to treatments, both individually and in combination. Using this model, our laboratory has previously demonstrated that the growth of several human adenocarcinomas can be inhibited by Apo2L/TRAIL. Apo2L/TRAIL triggers apoptosis in many types of tumor cells, and when combined with various chemotherapeutic agents results in enhanced inhibition of tumor growth in many xenograft models. To gain further insight into the antitumor potential of Apo2L/TRAIL in combination with chemotherapy, we compared the responses of 2 human colon adenocarcinomas, both of which were sensitive to CPT-11 while one was sensitive and the other comparatively resistant to Apo2L/TRAIL. In both cases, a greater degree of growth inhibition was achieved when these agents were used in combination. Western blot analysis demonstrated that in the Apo2L/TRAIL-sensitive tumor total cellular expression of Apo2L/TRAIL death receptors (DR4 and DR5) as well as protein expression of the pro-apoptotic molecule BAX were higher and the anti-apoptotic molecule Bcl-2 was lower in comparison to the Apo2L/TRAIL-resis...Continue Reading

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Citations

Oct 30, 2009·Southern Medical Journal·Constantin A DasanuDoru T Alexandrescu
Jan 15, 2014·Cytokine & Growth Factor Reviews·Pamela M Holland
Aug 19, 2014·Trends in Pharmacological Sciences·Sahdeo PrasadBharat B Aggarwal
Jun 18, 2009·Seminars in Immunopathology·Nadia CorazzaChristoph Lauer
Nov 8, 2015·Advanced Drug Delivery Reviews·Chaoliang HeXuesi Chen
Dec 1, 2010·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Peter Ujhazy, Edward B Garon
Sep 8, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Bonnie L HylanderElizabeth A Repasky
Nov 30, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Renata KontekKsenia Matlawska-Wasowska
Mar 4, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jeffrey WiezorekJonathan Graves

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