【摘要】 目的:通过动态观察新辅助动脉化疗前后子宫内膜癌细胞凋亡、细胞增殖以及耐药基因的变化,探讨子宫动脉持续灌注化疗的机理,为化疗后最佳手术时间的选择提供实验依据。方法:20例子宫内膜癌患者在术前行子宫动脉持续灌注5天,顺铂100mg、阿霉素50mg。分别于化疗前、化疗结束、化疗后1周、后2～2+3周和3+3～4周时取肿瘤组织。用TUNEL结合形态学方法检测细胞凋亡,用SABC法检测增殖细胞核抗原PCNA的表达,RT-PCR法测多药耐药基因MDR1、多药耐药相关基因MRP和肺耐药相关基因LRPmRNA的表达。结果:化疗结束时、化疗后1周和后2～2+3周时的AI均显著高于化疗前。化疗后AI/PI亦逐渐升高,至化疗后2～2+3周时最高。而化疗后3+3～4周时的AI和AI/PI均降至低于化疗前水平(P<0.05)。MDR1、MRP和LRP的表达在化疗后均有暂时性的一定程度的下降,于化疗后3+3～4周时升高且略高于化疗前水平,但与化疗前无显著性差异(P>0.05)。结论:术前子宫动脉持续灌注不仅可抑制细胞增殖活性,更主要的是促进细胞凋亡。评价子宫动脉化疗的疗效不能简单按细胞凋亡的变化,而必须结合化疗后的具体时间和PCNA的变化。化疗后3周左右手术是最合适的。更多还原

【Abstract】 Objective:Through investigating the influence of neoadjuvant intraarterial infu-sion chemotherapy(NIAC)on the timing changes of apoptosis and PCNA and multiple drug resis-tance associated genes of endometrial cancer to study the mechanism of chemotherapy and select the best operation time.Methods :Twenty patients were subjected to neoadjuvant consecutive u-terine arterial infusion with CDDP100mg and ADM50mg.The biopsy of endometrial tumor tis-sues was done before?just finished and1?2～2 +3 w?3 +3 ～4w after chemotherapy.Apoptosis index(AI)was estimated by a combination of histologic and TUNEL assays,proliferative index(PI)was exam-ined by SABC immunohistochemical staining,while the mRNA expression of multidrug resistance1(MDR1),multidrug resistance-associated protein(MRP)and lung resistance protein(LRP)were de-tected by reverse transcription polymerase chain reaction(RT-PCR).Results:The AI of endometri-al cancer cells just finished and1?2～2 +3 w after chemotherapy were all much higher than that be-fore chemotherapy.After chemotherapy,AI /PI gradually increased.It was highest in2～2 +3 w,while3 +3 ～4w after chemotherapy the AI and AI /PI were both significantly lower than that before chemotherapy.The expression of MDR1?MRP and LRP all temporarily decreased after chemother-apy,while3 +3 ～4w after chemotherapy they all increased to levels higher than that before chemotherapy,but the difference was not significant (P>0.05).Conclusion:Neoadjuvant consecu-tive intra-arterial infusion chemotherapy via uterine artery can inhibit tumor cell proliferation,and what is more important,it can induce the apoptosis effectively.To analyze the response of intraar-terial chemotherapy could’nt simply depend on the change of apoptosis index,but must connect with the time and cell proliferation.The most suitable time for the operation is3weeks after in-traarterial infusion chemotherapy.更多还原