R-Flurbiprofen Reverses Multidrug Resistance, Proliferation and Metastasis in Gastric Cancer Cells by p75NTR Induction

Citations Over TimeTop 16% of 2009 papers

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 receptor (p75(NTR)) in gastric cancer cells. The anticancer effects of R-flurbiprofen were found to require induction of p75(NTR) via the p38 signaling pathway, suggesting a possible mechanism of action.

Related Papers

• → miR-198 Represses the Proliferation of HaCaT Cells by Targeting Cyclin D2(2015)24 cited
• → gga‑microRNA‑375 negatively regulates the cell cycle and proliferation by targeting Yes‑associated protein 1 in DF‑1 cells(2020)4 cited
• Regulation of Qipiyin on the Cell Proliferation and Cell Cycle of Keratinocyte(2011)
• Effects of all-trans retinoic acid on cell cycle and proliferation of MCF-7 and expression of restin(2006)
• → miR-20b promotes cell growth in gastric cancer(2014)