Inhibiting the ERK pathway and the TRPM7 ion channel in gastric and bladder cancer cells

Abstract

Gastric and bladder cancers occur when the cells start to reproduce uncontrollably, starting within the innermost layer of tissue. The transient receptor potential cation subfamily M member 7 (TRPM7) is an ion channel that plays an important role in the survival of both of these cancers. In addition, extracellular regulated kinases (ERKs) contribute to the carcinogenesis of many cancers including gastric cancer. Therefore, the treatments Ginsenoside Rd, NS8593, curcumin, and icariin that have the ability to inhibit TRPM7 and ERK could potentially be used as a treatment for these cancers. We hypothesized that these treatments would decrease proliferation and induce apoptosis by inhibiting TRPM7 and ERK in AGS gastric cancer cells and T24 bladder cancer cells; the data supported the hypothesis. Individually, the overall most effective treatment was NS8593 which reduced the proliferation by 81.1% and increased apoptosis by 38.5% in AGS cells compared to the negative control. Individually, the overall most effective treatment was NS8593 which reduced the proliferation by 88.4% and increased apoptosis by 78.0% in T24 cells compared to the negative control. Using all the treatments in combination was the most effective in reducing proliferation and increasing apoptosis in gastric cancer cells. There was also a correlation between the TRPM7, extracellular regulated kinases (ERKs), proliferation, and apoptosis levels. These results could pose in future more effective treatments for both gastric and cancer on top of other types of cancers that rely on TRPM7 and ERK.