Possible Interaction: Tretinoin and Gemcitabine

“ Retinoic acid targets stellate cells which are part of the stroma and can thus augment the delivery of gemcitabine.”

“In conclusion, the antitumor effects of ATRA and its synergism with gemcitabine are associated with downregulation of PAKs.”

“The combination of ATRA and gemcitabine synergistically reduced cell growth in both wild-type and gemcitabine-resistant cell lines.”

“The combination of ATRA and gemcitabine synergistically reduced cell growth in both wild-type and gemcitabine-resistant pancreatic ductal adenocarcinoma cells.”

“In two distinct sets of organotypic models as well as KPC mice, we demonstrate a reduction in cancer cell proliferation and invasion together with enhanced cancer cell apoptosis when ATRA is combined with gemcitabine , compared to vehicle or either agent alone.”

“Furthermore, there was an indication that the combination of ATRA and gemcitabine caused increased apoptosis in vivo.”

“ ATRA decreased the half‐maximal inhibitory concentration (IC50) of gemcitabine by 2.8‐fold (ATRA‐non‐treated cells, 28.8 nM; ATRA‐treated cells, 10.0 nM).”

“The ATRA concentration of 0.03 &mgr;M was sufficient to enhance gemcitabine cytotoxicity, and the effect … well maintained in the concentration range from 0.03 to 50 &mgr;M. These results indicate that ATRA enhances gemcitabine cytotoxicity by increasing dCK expression in gemcitabine‐resistant human pancreatic cancer cells.”

“ Retinoic acid induces a G0/G1 arrest and combined with gemcitabine increases the apoptotic effect produced by chemotherapy probably as a consequence of a regulation of specific stem cell transcription factors.”