新辅助动脉化疗对子宫内膜癌细胞凋亡和耐药性的影响

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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。 OBJECTIVE: To investigate the mechanism of uterine artery continuous infusion chemotherapy by observing the changes of apoptosis, cell proliferation and drug resistance genes in neoadjuvant arteries before and after chemotherapy, and to provide experimental evidence for choosing the optimal operation time after chemotherapy. Methods: Twenty patients with endometrial cancer underwent continuous perfusion of uterine artery for 5 days, 100 mg of cisplatin and 50 mg of doxorubicin. The tumor tissues were taken before chemotherapy, at the end of chemotherapy, 1 week after chemotherapy, 2 ~ 2 + 3 weeks and 3 + 3 ~ 4 weeks after chemotherapy. Cell apoptosis was detected by TUNEL assay and PCNA expression was detected by SABC method. The expression of multidrug resistance gene MDR1, multidrug resistance-related gene MRP and lung resistance-related gene LRPmRNA were detected by RT-PCR. . Results: At the end of chemotherapy, the AI ​​at 1 week and 2 ~ 2 + 3 weeks after chemotherapy were significantly higher than those before chemotherapy. After chemotherapy AI / PI also gradually increased to 2 to 2 + 3 weeks after chemotherapy the highest. AI and AI / PI at 3 + 3 to 4 weeks after chemotherapy decreased to below pre-chemotherapy levels (P <0.05). The expression of MDR1, MRP and LRP all decreased temporarily after chemotherapy, and increased slightly and slightly higher than that before chemotherapy (P <0.05), but no significant difference was found between 3 and 3 to 4 weeks after chemotherapy ). Conclusion: Perioperative uterine artery perfusion can not only inhibit cell proliferation activity, but also promote apoptosis. Evaluation of the efficacy of uterine artery chemotherapy can not simply press the change of apoptosis, but must be combined with the specific time after chemotherapy and PCNA changes. About 3 weeks after surgery is the most appropriate surgery.
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