RIG-G基因抑制肺腺癌细胞增殖的作用与机制

我们的前期研究发现RIG-G是一个重要的肿瘤抑制基因，促进细胞周期停滞是其抑制肿瘤细胞增殖的机制。近来证实RIG-G在肺癌中具有极大的诱导表达潜力，同时又发现细胞周期的上调是肺癌细胞增殖的重要原因。推测RIG-G有望用于肺癌的增殖控制。为此，本研究拟以肺腺癌为研究对象，采用Tet-off表达系统和RNA干扰转染技术上调/下调细胞RIG-G的表达，分别检测转染肿瘤细胞的增殖能力；随后借助蛋白质芯片和western blot 技术检测转染肿瘤细胞增殖信号等重要信号分子和信号转导通路的表达与活化；进而利用染色体免疫沉淀，免疫共沉淀，荧光素酶报告基因，凝胶过滤层析等细胞和分子生物学技术研究RIG-G在肺腺癌细胞中抗肿瘤作用的分子机制；最后明确RIG-G对小鼠肺癌模型肿瘤细胞生长的抑制作用。为阐明RIG-G抗肺癌增殖的作用、机制与应用价值提供实验依据。

We previously reported the retinoic acid-induced gene G (RIG-G) was an important tumor inhibition gene, which induced growth arrest through inhibition of cell cycle in tumor cells. Preliminary experiments demonstrated that the expression of RIG-G could be induced remarkably in lung tumor cells; and up-regulation of cell cycle was strongly associated with the proliferation of lung cancer cells. Therefore,we speculate RIG-G is likely to inhibit the proliferation of lung cancer. First of all this study is to investigate tumor growth inhibitory function of RIG-G in lung adenocarcinoma cells via up/down-regulation of RIG-G gene expression with transfection technique of Tet-off expression system and RNAi; and then to analyze expression and activation of several important signaling molecules and signaling pathways such as proliferative signalling in transfected tumor cells through protein array and western blot; moreover, to research the molecular mechanisms of tumor inhibitory effect of RIG-G in lung adenocarcinoma cells via cellular and molecular biology techniques containing CHIP, CO-IP, Luciferase reportor assay, and gel filtration chromatography etc; finally, to confirm the tumor inhibitory effect of RIG-G in a lung cancer mouse model. This study will afford experiemental basis to elucidate the effect, mechanism, and applied value of RIG-G in anti-lung tumor proliferation.