摘要
目的探讨趋化因子基质细胞衍生因子-1（SDF-1）及趋化因子受体4（CXCR4）对胃癌腹膜转移潜能的影响。方法采用逆转录多聚酶链式反应（RT-PCR）检测胃癌细胞NUGC4及间皮细胞HMrSV中CXCR4和SDF-1 mRNA的表达。采用MTT实验检测NUGC4细胞增殖能力的变化，采用间皮细胞黏附实验及间皮细胞迁移实验评价体外培养的NUGC4细胞与间皮细胞发生黏附的能力及其穿越间皮细胞发生迁移的能力。通过建立裸鼠胃癌腹膜种植瘤模型，评价NUGC4细胞腹膜肿瘤生成能力及荷瘤裸鼠生存时间的变化。结果NUGC4细胞表达较高强度的CXCR4 mRNA，而间皮细胞表达高强度的SDF-1mRNA。抗CXCR4单抗对NUGC4细胞增殖具有显著的抑制作用（P〈0．05）；SDF-1可促进NUGC4细胞与间皮细胞黏附及穿越间皮细胞发生迁移，抗CXCR4单抗处理可显著抑制NUGC4细胞的黏附及迁移能力（P〈0．05）。体内实验结果显示，CXCR4拮抗剂AMD3100治疗组裸鼠的平均生存时间显著长于对照组[（43．8±2．8）vs（28．2±2．5）d，P〈0．01]，瘤结节数目显著低于对照组[（64．6±8．2）vs（103±12．4），P〈0．01]。结论趋化因子SDF-1及其受体CXCR4参与胃癌腹膜转移过程，与肿瘤细胞增殖、肿瘤细胞-间皮细胞间的黏附和肿瘤细胞迁移等步骤密切相关；干扰SDF-1／CXCR4生物学轴可以作为胃癌腹膜转移的潜在治疗策略。
Objective To investigate the effect of chemokine stromal cell-derived factor-1 （ SDF-1 ） and its receptor CXCR4 on the peritoneal carcinometastasis of gastric cancer. Methods Human gastric cancer cells of the lie NUGC4 and mesothelial cells of the line HMrSV were cultured. RT-PCR was used to detect the expression of CXCR4 and SDF-1 mRNA in the NUGC4 and HMrSV cells. The proliferation of NUGC4 cells was detected by MTT method. In mesothelial cell adhesion teat NUGC4 cells were cultured with confluent HMrSV mesothelial cells in 24-well plate and then divided into 3 groups： chemokine group, added with SDF-1, antibody blocking group, in which the NUGC4 cells were pre-incubated with CXCR4 monoclonal antibody for 2 h and then SDF-1 was added, and control group added with only culture fluid. Microscopy was used to calculate the number of gastric cancer cells adhered with mesothelial cells. In the mesothelial cell migration test HMrSV cells were put in the upper chamber of a Transwell chamber so as to cover the infiltration membrane. This Transwell chamber was put into a culture plate, NUGC4 cells, divided into 3 groups as mentioned above were put into the upper chamber, 24 h later HE staining and microscopy were performed to calculate the number of the NUGC4 cells that penetrated the membrane. BALB/c nu/nu female nude mice underwent intraperitoneal injection of NUGC4 cells , and then with PBS or AMD3100, small molecular specific antagonist, one day after the cancer cell injection once a day for 2 weeks. Then the mice were killed to observe the intraperitoneal tumorogenesis. Results CXCR4 mRNA was highly expressed in the NUGC4 cells but only very weekly expressed in the HMrSV cells. SDF-1 mRNA expression was seen in the HMrSV cells but in the NUGC4 cells. Anti-CXCR4 monoclonal antibody （McAb） inhibited the proliferation of NUGC4 cells significantly（P 〈 0. 05 ）. In mesothelial cell adhesion test, the number of the NUGC4 cells adhered with HMrSV cells after SDF-1 stimulation was 84. 4 ± 21.2, significantly
出处
《中华医学杂志》
CAS
CSCD
北大核心
2008年第3期202-205,共4页
National Medical Journal of China
关键词
胃肿瘤
肿瘤转移
腹膜
趋化因子
受体
Stomach neoplasms
Neoplasm metastasis
Peritoneum
Chemotatic factors
Receptor
