R-flurbiprofen reverses multidrug resistance, proliferation and metastasis in gastric cancer cells by p75(NTR) induction

Molecular Pharmaceutics
Haifeng JinDaiming Fan

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) can inhibit cell growth and metastasis, and induce cell apoptosis in cancerous cells. They have been shown to reduce incidence and mortality of gastric cancer by an unknown mechanism. NSAIDs often exert their effects by Cox-2 inhibition, and Cox-2 is overexpressed in gastric cancer cells. Nevertheless, when gastric cancer cells were treated with different NSAIDs, the non-Cox-2-inhibiting R-flurbiprofen was most effective at reducing proliferation of gastric cancer cells in vitro. R-Flurbiprofen prevented the metastatic characteristics of gastric cancer cells in vitro, and reduced tumor size and metastasis in vitro, when gastric cancer cells were injected into nude mice. R-Flurbiprofen also affected multidrug resistance, increasing the sensitivity of resistant gastric cancer cells to chemotherapeutic agents. Mechanistically, R-flurbiprofen was found to have pleiotropic effects, changing levels of cell cycle factors like Cyclin D1 and CKD4, apoptotic protwins like caspase3 and Bcl-2, and protwins that affect metastasis, like metalloproteases. Consistent with reports on other cancer cell types, NSAID treatment with R-flurbiprofen increased levels of the tumor suppressor neurotrophin re...Continue Reading

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Citations

Dec 7, 2010·Journal of Materials Science. Materials in Medicine·Saurabh VijayDipak K Majumdar
Oct 14, 2014·Drug and Chemical Toxicology·Taygun Timocin, Hasan B Ila
Jan 8, 2016·Drug and Chemical Toxicology·Taygun TimocinMehmet Topaktas
Jan 7, 2015·Applied Biochemistry and Biotechnology·Tomasz SiódmiakMichał Piotr Marszałł
Mar 3, 2011·Bioscience Reports·Michele Carrett-DiasGilma Santos Trindade

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