化疗后残余胃癌细胞发生上皮间质转化的体外研究

  目的  观察体外化疗能否诱导胃癌细胞发生上皮间质转化（epithelial mesenchymal transition，EMT）。   方法  使用5-Fu（30 μg/mL）对胃癌细胞株SGC7901进行4个疗程的体外化疗，残余细胞继续培养，得到能稳定传代的细胞SGC7901/Fu。比较SGC7901及SGC7901/Fu在细胞形态、EMT标记物、化疗耐药性、侵袭能力、肿瘤干细胞特性等方面的差异。   结果   与SGC7901比较，SGC7901/Fu呈间质细胞形态、上皮表型标记物表达下调、间质表型标记物表达上调。在SGC7901细胞及SGC7901/Fu细胞中，5-Fu的中效浓度（IC₅₀）分别为（43.8±7.2）μg/mL及（64.6±5.5）μg/mL，穿过Transwell小室基底膜的细胞数分别为（51.4±8.7）个及（93.2±9.5）个，克隆形成率分别为5.2%±1.0%及13.2%±2.2%，CD44+/CD24-细胞亚群所占比例分别为4.13%±0.81%及7.97%± 0.50%，两者间的差异均具有统计学意义（P<0.05）。   结论  体外化疗后残余的胃癌细胞发生EMT，同时细胞侵袭能力增强、化疗耐药性升高，并获得了肿瘤干细胞特性。 

Epithelial-mesenchymal transition in residual gastric cells after chemotherapy:An in vitro study

  Objective   To investigate if in vitro chemotherapy can induce the EMT progress in gastric cancer (GC) cells.   Methods  The GC cell line, SGC7901, was treated using 5-Fu at a concentration of 30 μg/mL. The residual cells after four cycles of 5-Fu therapy were named as SGC7901/Fu. The morphological changes and malignant biological features, including the invasiveness and clone formation ability and the characteristics of cancer stem cell and biomarkers of EMT between SGC7901 and SGC7901/Fu, were compared.   Results   The SGC7901/Fu cells displayed a mesenchymal appearance, decreased the expression of epithelial markers, and increased the expression of mesenchymal markers. The 50% inhibitory concentrations in the SGC7901/Fu and SGC7901 cells were (43.8±7.2) and (64.6±5.5) μg/mL, respectively. The number of cells that migrated through the basement-membrane of the Transwell chamber was 51.4±8.7 and 93.2±9.5, respectively. The rate of clone formation was 5.2%±1.0% and 13.2%±2.2%, respectively. The portions of the CD44+/CD24- cells were 4.13%±0.81% and 7.97%±0.50%, respectively. All differences were statistically significant (P< 0.05).   Conclusion   The residual GC cells underwent EMT progress after 5-Fu treatment, with increased chemoresistance and ability of invasiveness and acquired the property of cancer stem cells.