低氧环境下merlin-1蛋白对胃癌细胞黏附能力及细胞骨架表达调节的影响

Regulatory effect of merlin-1 on adhesion/metastasis and cytoskeleton remodeling in gastric cancer cells under hypoxia

目的:研究低氧条件下,merlin-1蛋白对汉族、回族和藏族胃癌细胞增殖、黏附能力及细胞骨架表达的调节作用,同时比较常氧或低氧条件下,merlin-1蛋白的作用是否具有民族特异性.方法:用MTT方法检测常氧或低氧条件下,merlin对回族、藏族和汉族胃癌原代细胞增殖及黏附、侵移的影响;免疫荧光染色法检测常氧或低氧条件下merlin对汉族、回族和藏族胃癌细胞骨架、细胞形态及细胞表面微绒毛表达的影响.同时分析merlin在常氧或低氧条件下的影响作用是否具有民族特异性.结果:常氧或低氧条件下,merlin-1蛋白均对汉族(P常氧=0.00,P低氧=0.00)、回族(P常氧=0.00,P低氧=0.00)和藏族(P常氧=0.00,P低氧=0.00)胃癌细胞增殖均有明显的抑制作用,但merlin-1对不同民族胃癌细胞增殖的抑制作用无民族特异性(P常氧>0.05,P低氧>0.05).黏附能力检测结果显示,在常氧及低氧条件下merlin-1蛋白对汉族(P常氧=0.00,P低氧=0.00)、回族(P常氧=0.00,P低氧=0.00)和藏族(P常氧=0.00,P低氧=0.00)胃癌细胞黏附能力均有抑制作用,且抑制能力亦无民族特异性[P常氧=0.51(3 h)、0.07(48 h),P低氧=0.47(3 h)、0.17(48 h)].在对细胞骨架、细胞形态变化及细胞微绒毛表达实验中,观察到merlin-1在低氧条件下可加强细胞骨架表达.结论:低氧条件对merlin-1抑制回族、藏族和汉族胃癌细胞增殖能力无明显影响,且merlin-1蛋白对胃癌细胞的抑制能力无论在常氧或低氧条件下,均无民族特异性.merlin蛋白在低氧条件下对胃癌细胞骨架表达有促进作用.

AIM： To investigate the regulatory effect of mer- lin-1 on cell proliferation, adhesion/metastasis and cytoskeleton remodeling in gastric cancercells under hypoxia from Qinghai Han-, Hui- and Tibetan-ethnic patients, and to study if the function of merlin-1 in different ethnic groups is related to ethnic specificity under normoxic or hypoxic conditions.METHODS： MTT assay was used to analyze the influence of merlin-1 on the cell prolifera- tion, adhesion/metastasis and motility, and immunofluorescence staining was performed to detect cytoskeleton remodeling, morphologi- cal changes, and the distribution of microvilli on the surface of gastric cancer cells from Han-, Hui- and Tibetan-ethnic patients. In addition, we explored whether the function of merlin-1 in different ethnic groups is correlated with ethnic specificity under normoxic or hypoxic conditions.RESULTS： The proliferation of gastric cancer cells from Han-, Hui- and Tibetan-ethnic groups was inhibited by merlin-1 under both normoxic and conditions （Pnormoxic = 0.00, 0.00, 0.00; Pnormoxic = 0.00, 0.00, 0.00）, and the influence of merlin-1 on cancer cell proliferation was not related to eth- nic specificity （Pnormoxic 〉 0.05; Pnormoxic 〉 0.05）. The results of adhesion/metastasis analysis showed that merlin-1 inhibited the adhesion/metastasis ability of gastric cancer cells from Han-, Hui- and Tibetan-ethnic groups under both normoxic and hypoxic conditions （Pnormoxic= 0.00, 0.00, 0.00; Pnormoxic = 0.00, 0.00, 0.00）, and the inhibitory effect of merlin-1 in three ethnic groups showed no significant differences [Pnormoxic = 0.51 （3 h）, 0.07 （48 h）; Pnormoxic=0.47 （3 h）, 0.17 （48 h）]. By detec- tion of cytoskeleton remodeling, morphological change and microvilli distribution, it was found that merlin-1 enhanced cytoskeleton remodeling under hypoxic conditions compared with nor- moxic conditions.CONCLUSION： Merlin-1 can inhibit the pro- liferation and adhesion/metastasis of gastric cancer cells under both hypoxic and normoxic conditions, which is independent on the ethnic- ity of patients from whom gastric cancer ceilsare obtained. However, merlin-1 enhances cyto- skeleton remodeling under hypoxic conditions.