吡柔比星与温热协同对胃癌组织的体外作用

Chemotherapy Effects of Pirarubicin in Combination with Hyperthermia on Gastric Cancer Tissues in Vitro

目的比较吡柔比星(Pirarubicin,THP)和其他化疗药物对胃癌组织温热协同的作用,探讨化疗药物与温热化疗的协同作用机制。方法利用36个病例的手术切除胃癌组织,建立人胃癌组织体外立体培养作用模型,MTS-PMS比色法检测组织培养物活性以了解化疗药物以及温热化疗的抑瘤效果。TUNEL荧光检测原位细胞凋亡,HE染色研究评价药物对胃癌组织在组织形态学上的改变并进行电镜观察。结果DDP、MMC和THP对胃癌组织的杀伤均具有较强的温热协同关系(P=0.000),THP单独处理和温热协同处理均具有较强的抑制作用,和其他3种药物抑制率比较具有显著性差异(P<0.05)。THP和温热协同处理效果和胃癌病例组织学分级有关(P=0.000),而与年龄、性别、肿瘤大小、临床分期和术前CEA水平无关(P>0.05)。THP温热协同处理凋亡指数和其他3种药物比较具有显著性差异(P<0.05)。HE染色表明,THP和温热处理后,胃癌组织大部崩解,细胞变性坏死。电镜分析表明经THP和温热协同处理后细胞胞膜内陷,胞浆空泡化,并出现染色质浓聚,同时核膜消失。结论THP对胃癌组织具有良好的温热协同效应和肿瘤杀伤效果,具有进一步临床研究价值。

Objective Comparison of the effects of pimrubicin （THP） in combination with hyperthermia on gastric cancer tissues in vitro and to discuss the underlying mechanisms.Methods In vitro three-dimensional acting models were established with tissue biopsies from 36 patients with pathologically confirmed gastric cancer. Tumor cell viability was measured by MTS-PMS assay, TUNEL fluorescence detection in situ apoptosis,HE staining was used to study histomorphology of drug treated gastric tissues. Electron microscope observed cells. Remits Synergistic effects were observed after tumor tissues were treated with hyperthermia and three drugs including cisplatin,THP, and mitomycin （P=0. 000）,while THP exhibited superior cytotoxic effects to other drugs on cancer tissues. Furtherrnore,histomorpholcgical studies suggested strong killing effects of THP on cancer tissues, including disrupted tissue structure,cellular degradation and necrosis,karyopyknosis and karyolysis, also with loss of cytoplasm. Antitumoral effects of THP were associated with pathological grading（P = 0. 000）,while irrelated to patients＇ gender, age,tumor size,clinical staging and preoperative CEA levels（P〉0. 05）. The apoptosis index has significant difference compared THP and the other three drugs, After treated by THP,the gastric tissues disaggregation, and electron microscope observed cell membrane invagination, endochylema vacuolization. Nuclear membrane diaappeared. Conclusion Synergistic effects of pirarubicin in combination with hyperthermia were evident; cytotoxicity of pirarubicin was thermally enhanced considerably by mild hyperthermia on gastric cancer tissue. THP may be a potential therapeutic drug for intra-peritoneal chemohypertherrnia.