Previous studies have indicated that capsaicin-rich diet and cold weather have shown strong association with tumor incidence. Thus, we investigated the effects of capsaicin and cold exposure in 1,2-dimethylhydrazine (DMH)-induced colorectal cancer as well as the mechanisms underlying capsaicin and cold-induced CRC. Rats were randomly divided into four groups and received cold still water and capsaicin via intragastric gavage until the end of the experiment. The rat’s body weight, thymus weight, and food intakes were assessed. Global levels of histone H3K9, H3K18, H3K27, and H4K16 acetylation and histone deacetylase (HDACs) in colon mucosa were assessed by western blot. Expression levels of Toll-like receptors 2 (TLR2) and Toll-like receptors 4 (TLR4) were measured by western blot and reverse-transcriptase quantitative polymerase chain reaction (qPCR). We found that cold and low-dose capsaicin increased tumor numbers and multiplicity, although there were no differences in tumor incidence. Additionally, rat exposure to cold water and capsaicin display further higher levels of histone H3 lysine 9 (H3K9AC), histone H3 lysine 18 (H3K18AC), histone H3 lysine 27 (H3K27AC), and HDACs compared with the DMH and normal rats. In contrast, a considerable decrease of histone H4 lysine 16 (H4K16AC) was detected in the colon mucosa. Cold and low-dose capsaicin exposure groups were also increased TLR2 and TLR4 protein levels and mRNA levels. These results suggest that chronic cold exposure and capsaicin at a low-dose intervention exacerbate ectopic expression of global histone acetylation and TLR level, which are crucial mechanisms responsible for the progression of colorectal cancer in rats.

先前的研究表明，富含辣椒素的饮食和寒冷的天气与肿瘤发病率密切相关。因此，我们研究了辣椒素和冷暴露在 1,2-二甲基肼 (DMH) 诱导的结直肠癌中的影响，以及辣椒素和冷诱导的 CRC 的潜在机制。将大鼠随机分为四组，灌胃给予冷水和辣椒素直至实验结束。评估大鼠的体重、胸腺重量和食物摄入量。通过蛋白质印迹评估结肠粘膜中组蛋白 H3K9、H3K18、H3K27 和 H4K16 乙酰化和组蛋白去乙酰化酶 (HDAC) 的整体水平。通过蛋白质印迹和逆转录酶定量聚合酶链反应 (qPCR) 测量 Toll 样受体 2 (TLR2) 和 Toll 样受体 4 (TLR4) 的表达水平。我们发现冷和低剂量辣椒素增加了肿瘤数量和多样性，尽管肿瘤发病率没有差异。此外，与 DMH 和正常大鼠相比，暴露于冷水和辣椒素的大鼠显示出更高水平的组蛋白 H3 赖氨酸 9 (H3K9AC)、组蛋白 H3 赖氨酸 18 (H3K18AC)、组蛋白 H3 赖氨酸 27 (H3K27AC) 和 HDAC。相反，在结肠粘膜中检测到组蛋白 H4 赖氨酸 16 (H4K16AC) 的显着减少。冷和低剂量辣椒素暴露组的 TLR2 和 TLR4 蛋白水平和 mRNA 水平也增加。