异黏蛋白调控鼻咽癌细胞增殖及紫杉醇耐药的研究

目的探讨异黏蛋白(Metadherin, MTDH)对鼻咽癌细胞增殖及紫杉醇耐药的影响。方法采用慢病毒介导的MTDH cDNA和MTDH-shRNA转染鼻咽癌细胞,分别上调和抑制MTDH的表达。CCK-8法、流式细胞实验分别检测细胞增殖能力、细胞周期及凋亡改变。CCK-8法确定紫杉醇对鼻咽癌细胞的IC₃₀、IC₅₀、IC₇₀,并检测IC₃₀、IC₅₀、IC₇₀浓度下MTDH过表达组与沉默组细胞生存率改变。结果 MTDH上调后5-8F、HNE-1细胞的增殖能力均增强,而沉默MTDH后细胞的增殖能力均降低。MTDH沉默组的G1期细胞比例明显增加。MTDH过表达组细胞凋亡率降低,MTDH沉默组细胞凋亡率增加。MTDH表达上调之后,鼻咽癌细胞对紫杉醇的敏感度降低,在IC₇₀、IC₅₀浓度下,MTDH过表达组细胞的生存率高于对照组细胞。沉默MTDH之后,鼻咽癌细胞对紫杉醇的敏感度升高,在IC₅₀、IC₃₀浓度下,MTDH沉默组细胞的生存率低于对照组细胞。结论 MTDH在促进鼻咽癌细胞增殖中起重要作用,其高表达可促进鼻咽癌细胞紫杉醇耐药性的产生。

Metadherin-mediated Cell Proliferation and Paclitaxel Resistance in Nasopharyngeal Carcinoma

Objective To explore the effect of metadherin (MTDH) on cell proliferation and paclitaxel resistance in nasopharyngeal carcinoma (NPC) patients. Methods The expression of MTDH was upregulated and inhibited by lentivirus-mediated MTDH cDNA and MTDH-shRNA in NPC cells, respectively. Cell proliferation, cell cycles and apoptosis were examined by CCK-8 and flow cytometry. The IC_30,IC_50,IC₇₀value of paclitaxel in NPC cells were obtained by CCK-8 assay. Then, the survival rates of MTDH overexpression cells and MTDH silence cells, stimulated with paclitaxel at IC₃₀, IC₅₀ and IIC₇₀ were evaluated using CCK-8 assay. Results MTDH overexpression enhanced the proliferation abilities of 5-8F and HNE-1 cells, while MTDH silence inhibited the proliferation abilities and greatly increased cells in G1 phase. The apoptosis was decreased by MTDH overexpression, and promoted by MTDH silence. MTDH overexpression induced paclitaxel resistance. Compared with control group, survival rate of MTDH overexpression cells in the presence of paclitaxel at IC70 and IC50 was increased. On the contrary, MTDH silence sensitized NPC cells to paclitaxel. The survival rate of MTDH silence cells in the presence of paclitaxel at IC50 and IC30 was decreased. Conclusion MTDH plays an important role in promoting NPC cell proliferation, and the high expression of MTDH could induce paclitaxel resistance in NPC cells.