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/cnu/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)、门细胞介素-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.