Peng Yuanfei, Zheng Minhua, Feng Bo, Chen Xuehua, Yu Beiqin, Lu Aiguo, Wang Minliang, Li Jianwen, Ma Junjun, Xu Lie
Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China.
Oncol Rep. 2008 Jan;19(1):73-9.
Peritoneal carcinomatosis of colorectal cancer is common and associated with poor prognosis, which poses a serious challenge and satisfactory treatments are urgently needed. Hyperthermic CO2 pneumoperitoneum (HT-CO2) is a new strategy. This study was designed to determine the potential of HT-CO2 against colorectal cancer cells. Based on an in vitro HT-CO2 study model, the anti-tumor efficacy of HT-CO2 (42-44 degrees C for 2-4 h) on human colon cancer COLO 205 cells was evaluated and the mechanisms of actions were analyzed. We found that HT-CO2 (43-44 degrees C for 2-4 h) significantly decreased cell viability as determined by WST-8 assay, and the cytotoxicity was attributable to HT-CO2-induced hyperthermia and extracellular acidification. Apoptosis was the major form of cell killing as demonstrated by Annexin-V/PI flow cytometry and morphological analysis (Hoechst/PI fluorescence microscopy and transmission electron microscopy). Further Western blot analysis and flow cytometric analysis of mitochondrial membrane potential showed that Bax-associated mitochondrial apoptotic pathway played critical role in the induction of apoptosis. We conclude that HT-CO2 has significant cytotoxic effect on colon cancer cells through induction of Bax-associated mitochondrial apoptosis, and the cytocidal effect is attributable to HT-CO2-induced hyperthermia and extracellular acidifications. Our data suggest that HT-CO2 may serve as a potential candidate for treating and/or preventing peritoneal carcinomatosis of colorectal cancer and further investigations both in vitro as well as in vivo in animal models are needed.
结直肠癌腹膜转移很常见且预后较差，这构成了严峻挑战，迫切需要令人满意的治疗方法。高温二氧化碳气腹（HT-CO2）是一种新策略。本研究旨在确定HT-CO2对结直肠癌细胞的作用潜力。基于体外HT-CO2研究模型，评估了HT-CO2（42-44摄氏度，持续2-4小时）对人结肠癌COLO 205细胞的抗肿瘤疗效，并分析了其作用机制。我们发现，通过WST-8检测确定，HT-CO2（43-44摄氏度，持续2-4小时）显著降低细胞活力，且细胞毒性归因于HT-CO2诱导的热疗和细胞外酸化。通过Annexin-V/PI流式细胞术和形态学分析（Hoechst/PI荧光显微镜和透射电子显微镜）证明，凋亡是细胞死亡的主要形式。进一步的蛋白质免疫印迹分析和线粒体膜电位的流式细胞术分析表明，Bax相关的线粒体凋亡途径在凋亡诱导中起关键作用。我们得出结论，HT-CO2通过诱导Bax相关的线粒体凋亡对结肠癌细胞具有显著的细胞毒性作用，且细胞杀伤作用归因于HT-CO2诱导的热疗和细胞外酸化。我们的数据表明，HT-CO2可能作为治疗和/或预防结直肠癌腹膜转移的潜在候选方法，需要在体外以及动物模型体内进行进一步研究。
