CXC趋化因子受体4及基质细胞衍生因子1在宫颈癌组织中的表达及其与化疗药物敏感性之间的关系

Expression of CXC chemokine receptor 4 and stromal cell derived factor 1 in cervical cancer tissues and its relationship with sensitivity of chemotherapeutic drugs

目的研究CXC趋化因子受体4(CXCR4)及基质细胞衍生因子1(SDF)-1在宫颈癌组织中的表达情况,及其与宫颈癌常规化疗药物敏感性之间的关系。方法收集山西医科大学第一医院2017年6月至2018年6月手术切除的宫颈癌组织新鲜标本40例,采用MTT法检测原代培养宫颈癌细胞对顺铂、环磷酰胺、紫杉醇、5-氟尿嘧啶的体外药物敏感性,蛋白印迹法检测癌组织中CXCR4及SDF-1的表达情况,分析CXCR4及SDF-1的表达与药物敏感性之间的关系。结果不同宫颈癌细胞体外对化疗药物敏感性存在差异,紫杉醇,顺铂,5-氟尿嘧啶及环磷酰胺的平均抑制率分别为:65±11、52±10、32±12、19±7,差异有统计学意义(P<0.05);与癌旁组织相比,CXCR4及SDF-1在宫颈癌组织中的表达显著增高(P<0.05),CXCR4及SDF-1的表达与肿瘤的分化程度及临床分期有关(P<0.05)。CXCR4及SDF-1在紫杉醇耐药组中的表达显著高于敏感组(P<0.05),SDF-1在顺铂耐药组中的表达显著高于敏感组(P<0.05)。结论 MTT药敏实验对宫颈癌化疗药物的选择具有一定的参考价值,CXCR4及SDF-1在宫颈癌中表达上调,可能与紫杉醇及顺铂的耐药有关。

Objective To determine the expression of CXCR4 and SDF-1 in cervical cancer tissues and its relationship with sensitivity of conventional chemotherapeutic drugs for cervical cancer. Methods Forty fresh specimens of cervical cancer,which were surgically resected at the First Hospital of Shanxi Medical University between June 2017 and June 2018, were collected. The sensitivities of the primary cultured cervical cancer cells to the in vitro drugs(Cisplatin, Cyclophosphamide, Paclitaxel and 5-Fluorouracil) were examined by MTT assay. Western blotting was used to determine the expression of CXCR4 and SDF-1. The relationship between the expression of CXCR4 and SDF-1 and drug sensitivity was analyzed. Results There were differences in the sensitivity of different cervical cells to chemotherapeutic drugs.The average inhibition rates of Paclitaxel, Cisplatin, 5-Fluorouracil and Cyclophosphamide were 65±11, 52±10, 32±12, and 19±7, with statistically significant differences(all P<0.05). Compared with precancerous tissues, the levels of CXCR4 and SDF-1 in cervical cancer tissues significantly increased(both P<0.05). The expression levels of CXCR4 and SDF-1 were correlated with tumor differentiation and TNM stage(both P<0.05). The expression levels of CXCR4 and SDF-1 in the Paclitaxel-resistant group were significantly higher than those in the sensitive group(both P<0.05). The expression level of SDF-1 in the Cisplatin-resistant group was significantly higher than that in the sensitive group(P<0.05). Conclusion MTT susceptibility test provides certain reference for the selection of chemotherapeutic drugs for cervical cancer. The up-regulated CXCR4 and SDF-1 levels in cervical cancer may be related to the resistance of Paclitaxel and Cisplatin.