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

最近的研究表明，跨上皮离子转运在细胞增殖和细胞死亡等基本细胞功能中发挥着重要作用。特别是据报道，氯离子转运通过调节细胞体积来影响细胞增殖。此外，线粒体作为产生能量的细胞器具有极其重要的作用，已知受到细胞内离子环境的影响。本研究通过对氯离子通道和Na+/K+/2Cl-协同转运体(NKCC)的调节，研究氯离子转运是否调节肾上皮细胞A6细胞的增殖和线粒体的活性。用NPPB(氯离子通道阻滞剂)和Qercetin(NKCC调节剂)处理可抑制细胞生长和线粒体活性，但Bumetanide(NKCC抑制剂)不影响细胞生长和线粒体活性。我们已经报道，氯离子转运的调节剂会通过调节细胞内离子环境来影响细胞增殖和线粒体活性。基于这些结果，我们已经开始对人胃癌细胞株进行同样的检测，而不是青蛙肾上皮细胞。此外，我们还提取了幽门螺杆菌VacA毒素，以评估该毒素在本检测系统中的功能。另一方面，我们全面报道了有关人胃癌，特别是残胃癌的临床病理和遗传学分析，以供参考。这些研究项目将带来人类残胃癌的巨大进步。由JSPS 15659053(YM)，15590189(NN)，15790120(HM)支持

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)