吡柔比星在体外胃癌组织温热化疗中作用的研究

Effects of pirarubicin chemotherapy combined with hyperthermia on gastric cancer in vitro

目的比较吡柔比星和其他化疗药物的对胃癌组织温热协同作用,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。HE染色研究评价药物对胃癌组织在组织形态学上的改变。结果顺铂、丝裂霉素和吡柔比星对胃癌组织的杀伤均具有较强的温热协同关系(P=0.000),吡柔比星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)。吡柔比星和温热协同处理效果与胃癌病例的临床分期和组织学分级有关(P=0.000),而与年龄、性别、肿瘤大小及术前CEA水平无关(P>0.05)。HE染色表明,吡柔比星和温热处理后,胃癌组织大部崩解,细胞变性坏死,细胞核固缩,胞浆散失。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 To evaluate the effect ofpirarubicin （THP） in combination with hyperthermia on gastric cancer tissues in vitro and explore the underlying mechanisms. Methods In vitro three-dimensional culture models were established with tissue biopsies from 36 patients with pathologically confirmed gastric cancer. The tumor cell viability was measured by MTS-PMS assay, and HE staining was used to study the histomorphological changes of the tissues following chemotherapy and hyperthermia. Results Synergistic tumor cell-killing effects of cisplatin, THP, and mitomycin with hyperthermia was observed in the tumor tissues （P-=0.000）, and THP exhibited stronger cytotoxic effects than the other drugs. Histomorphological study suggested strong killing effects of THP on the tumor tissues, which displayed disrupted tissue structure, cellular degradation and necrosis, karyopyknosis and karyolysis, with cytoplasm loss. The anti-tumor effects of THP were associated with clinical staging and pathological grading of the tumors （P=-0.000）, but not with the patients＇ gender, age, tumor size and preoperative CEA levels （P〉0.05）. Conclusion Pirarubicin shows good synergistic effects with hyperthermia, and the cytotoxicity of pirarubicin against gastric cancer tissue is enhanced considerably by mild hyperthermia. THP can be a potential therapeutic drug for intraperitoneal chemohyperthermia.