质子泵抑制剂对SGC-7901胃腺癌裸小鼠癌性恶病质的作用

Effect of Proton Pump Inhibitors on Cancer Cachexia in Nude Mice Bearing SGC-7901 Gastric Adenocarcinoma

背景:癌性恶病质是癌症晚期最重要的并发症之一。质子泵抑制剂(PPIs)目前广泛用于治疗酸相关疾病,有研究显示其对恶性肿瘤细胞具有化疗增敏和诱导凋亡作用。目的:探讨PPIs对裸小鼠癌性恶病质的改善作用及其可能机制。方法:予BALB/c nu/nu裸小鼠皮下注射人胃腺癌细胞株SGC-7901建立癌性恶病质模型并予PPIs干预(奥美拉唑治疗组和泮托拉唑治疗组),同时设立不予干预的癌性恶病质组和非荷瘤空白对照组,每组11只裸小鼠。观察各组裸小鼠的一般情况、肿瘤体积以及与癌性恶病质的发生、发展密切相关的血清细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平。结果:两组PPI治疗组裸小鼠体质量下降受抑,摄食、饮水量明显高于癌性恶病质组,血清TNF-α、IL-6水平明显低于癌性恶病质组,差异均有统计学意义(P<0.05),肿瘤体积则与癌性恶病质组无明显差异。结论:PPIs对裸小鼠的癌性恶病质有明显改善作用,其机制可能与改变体内细胞因子水平有关。

Background： Cancer cachexia is one of the most important complications of advanced cancer. It has been reported that proton pump inhibitors （PPIs）, currently used in the treatment of acid-related diseases, can increase the sensitivity of cancer cells to cytotoxic agents and induce cancer cell apnptosis. Aims： To investigate the improvement effect of PPIs on cancer cachexia in nude mice and its possible mechanism. Methods： Thirty-three BALB/c nu/nu nude mice were injected with human gastric adenocarcinoma cell line SGC-7901 subcutaneously to induce cancer cachexia, and then randomized to receive omeprazole, pantoprazole or normal saline treatment （Ome-treated group, Pan-treated group, and cancer cachexia group）, respectively; 11 nude mice without any intervention served as blank controls. The general condition, tumor volume and the serum levels of two cachexia-associated cytokines, tumor necrosis factor-ct （TNF-α） and interleukin-6 （IL-6） were observed. Results： In two PPI-treated groups, the loss of body weight was inhibited, the food and water intake was increased when compared with the cancer cachexia group （P〈0.05）, whereas the serum levels of TNF-α and IL-6 were obviously decreased （P〈0.05）. No significantly differences were observed in tumor volume between PPl-treated groups and cancer cachexia group. Conclusions： PPIs have remarkable improvement effect on cancer cachexia in nude mice, which might be associated with the changes of cytokines levels.