The functional analysis of Helicobacter pylori VacA toxin on the proliferation of remnant stomach cancer

近年来的研究表明，上皮离子转运在细胞增殖和细胞死亡等基本细胞功能中起着重要作用。特别是，据报道氯离子转运通过调节细胞体积影响细胞增殖。此外，线粒体作为产生能量的细胞器具有极其重要的作用，已知其受细胞内离子环境的影响。在本研究中，我们研究氯离子转运是否通过氯离子通道和Na+/K+/2Cl-cotransporter （NKCC）调节肾上皮A6细胞的细胞增殖和线粒体活性。NPPB（一种氯离子通道阻滞剂）和槲皮素（一种NKCC调节剂）抑制细胞生长和线粒体活性，但布美他尼（一种NKCC抑制剂）对它们没有影响。我们已经报道氯离子运输的调节因子会通过调节细胞内离子环境影响细胞增殖和线粒体活性。基于这些结果，我们开始用人类胃癌细胞系代替青蛙肾上皮细胞进行同样的实验。我们还提取了幽门螺杆菌VacA毒素来评估毒素在这个检测系统中的功能。另一方面，我们全面报道了人类胃癌，特别是残胃癌的临床病理和遗传学分析，以供参考。这些研究项目将为人类残胃癌的研究带来巨大的进步。支持JSPS 15659053 (YM), 15590189 (NN), 15790120 （HM）

Recent studies show that transepithelial ion transport plays an important role in fundamental cellular functions such as cell proliferation and cell death. Particularly, chloride ion transport is reported to affect cell proliferation by regulating cell volume. In addition, mitochondria which have an extremely important role as energy-producing organella are known to be influenced by intracellular ion environments. In the present study, we studied whether chloride ion transport regulates cell proliferation and activity of mitochondria in renal epithelial A6 cells by using regulators of chloride ion channel and Na+/K+/2Cl-cotransporter (NKCC). Treatment with NPPB (a chloride ion channel blocker) and quercetin (an NKCC regulator) inhibited cell growth and activity of mitochondria, but bumetanide (an NKCC inhibitor) did not affect them. We have reported that regulators of chloride ion transport would influence cell proliferation and mitochondrial activity by regulating intracellular ion environments. Based on these results, we have started the same assay of human gastric cancer cell lines instead of frog renal epithelial cells. And also we have been extracting Helicobacter pylori VacA toxin to evaluate the function of the toxin in this assay system. On the other hand, we have reported the clinico-pathological and genetic analysis concerning human gastric cancer, especially remnant stomach cancer as references comprehensively. These research projects will bring the great advancement in human remnant stomach cancer.Supported by JSPS 15659053 (YM), 15590189 (NN), 15790120 (HM)