CONTEXT Obacunone, a limonoid abundantly found in Citrus fruits, exhibits a variety of bioactivities. OBJECTIVE To investigate the effects of obacunone on a colorectal cancer (CRC) mouse model, and clarify its potential molecular mechanisms. MATERIALS AND METHODS The male Balb/c mice were induced with azoxymethane and dextran sulfate sodium for 12 weeks. Obacunone (50 mg/kg) was administered via oral gavage three times every week until the end of the experiment. Disease indexes including body weight, spleen weight, bloody diarrhea, colon length, histopathological score, and tumor size were measured. The anti-proliferation activities of obacunone were analyzed by MTT or flow cytometry. The expression of protein and mRNA related to cell proliferation or inflammatory cytokines was determined by Western blot, q-PCR and IHC. RESULTS Obacunone significantly alleviated bloody diarrhea, colon shortening (7.35 ± 0.2128 vs. 8.275 ± 0.2169 cm), splenomegaly, histological score (9 ± 0.5774 vs. 6 ± 0.5774) and reduced tumor size (4.25 ± 0.6196 vs. 2 ± 0.5669). Meanwhile, the expression of protein and mRNA related to cell proliferation or inflammatory cytokines was remarkably decreased in tumor tissue. Obacunone inhibited the proliferation activities of colorectal cancer cells. Moreover, obacunone induced colorectal cancer cells G1 and G2 phases arrest, and suppressed the expression of cell cycle genes. CONCLUSIONS Obacunone could alleviate CRC via inhibiting inflammatory response and tumor cells proliferation. The results may contribute to the effective utilization of obacunone or its derivatives in the treatment of human CRC.

中文翻译：

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Obacunone 可减少慢性炎症诱导的结直肠癌小鼠的炎症信号传导和肿瘤发生

背景 Obacunone 是一种在柑橘类水果中大量发现的柠檬苦素，具有多种生物活性。目的研究奥巴松酮对结直肠癌（CRC）小鼠模型的影响，阐明其潜在的分子机制。材料和方法雄性Balb/c小鼠用偶氮甲烷和葡聚糖硫酸钠诱导12周。Obacunone (50 mg/kg) 每周 3 次通过口服管饲法给药，直到实验结束。测量疾病指标包括体重、脾重、血性腹泻、结肠长度、组织病理学评分和肿瘤大小。通过MTT或流式细胞仪分析奥巴库酮的抗增殖活性。通过蛋白质印迹、q-PCR和IHC检测与细胞增殖或炎性细胞因子相关的蛋白质和mRNA的表达。结果 Obacunone 显着减轻血性腹泻、结肠缩短（7.35 ± 0.2128 对 8.275 ± 0.2169 cm）、脾肿大、组织学评分（9 ± 0.5774 对 6 ± 0.5774）和减小肿瘤大小（4.25 ± 0.6196 对 2 ± 0.5669）。同时，肿瘤组织中与细胞增殖或炎性细胞因子相关的蛋白和mRNA表达明显降低。Obacunone 抑制结直肠癌细胞的增殖活性。此外，奥巴康酮诱导结直肠癌细胞G1期和G2期停滞，并抑制细胞周期基因的表达。结论奥巴松酮可通过抑制炎症反应和抑制肿瘤细胞增殖来缓解CRC。该结果可能有助于有效利用奥巴松酮或其衍生物治疗人类结直肠癌。结肠缩短（7.35 ± 0.2128 vs. 8.275 ± 0.2169 cm）、脾肿大、组织学评分（9 ± 0.5774 vs. 6 ± 0.5774）和肿瘤大小减小（4.25 ± 0.6196 vs. 2 ± 0.5669）。同时，肿瘤组织中与细胞增殖或炎性细胞因子相关的蛋白和mRNA表达明显降低。Obacunone 抑制结直肠癌细胞的增殖活性。此外，奥巴康酮诱导结直肠癌细胞G1期和G2期停滞，并抑制细胞周期基因的表达。结论奥巴松酮可通过抑制炎症反应和抑制肿瘤细胞增殖来缓解CRC。该结果可能有助于有效利用奥巴松酮或其衍生物治疗人类结直肠癌。结肠缩短（7.35 ± 0.2128 vs. 8.275 ± 0.2169 cm）、脾肿大、组织学评分（9 ± 0.5774 vs. 6 ± 0.5774）和肿瘤大小减小（4.25 ± 0.6196 vs. 2 ± 0.5669）。同时，肿瘤组织中与细胞增殖或炎性细胞因子相关的蛋白和mRNA表达明显降低。Obacunone 抑制结直肠癌细胞的增殖活性。此外，奥巴康酮诱导结直肠癌细胞G1期和G2期停滞，并抑制细胞周期基因的表达。结论奥巴松酮可通过抑制炎症反应和抑制肿瘤细胞增殖来缓解CRC。该结果可能有助于有效利用奥巴松酮或其衍生物治疗人类结直肠癌。5774）并减小肿瘤大小（4.25 ± 0.6196 对 2 ± 0.5669）。同时，肿瘤组织中与细胞增殖或炎性细胞因子相关的蛋白和mRNA表达明显下降。Obacunone 抑制结直肠癌细胞的增殖活性。此外，奥巴康酮诱导结直肠癌细胞G1期和G2期停滞，并抑制细胞周期基因的表达。结论奥巴松酮可通过抑制炎症反应和抑制肿瘤细胞增殖来缓解CRC。该结果可能有助于有效利用奥巴松酮或其衍生物治疗人类结直肠癌。5774）并减小肿瘤大小（4.25 ± 0.6196 对 2 ± 0.5669）。同时，肿瘤组织中与细胞增殖或炎性细胞因子相关的蛋白和mRNA表达明显降低。Obacunone 抑制结直肠癌细胞的增殖活性。此外，奥巴康酮诱导结直肠癌细胞G1期和G2期停滞，并抑制细胞周期基因的表达。结论奥巴松酮可通过抑制炎症反应和抑制肿瘤细胞增殖来缓解CRC。该结果可能有助于有效利用奥巴松酮或其衍生物治疗人类结直肠癌。Obacunone 抑制结直肠癌细胞的增殖活性。此外，奥巴康酮诱导结直肠癌细胞G1期和G2期停滞，并抑制细胞周期基因的表达。结论奥巴松酮可通过抑制炎症反应和抑制肿瘤细胞增殖来缓解CRC。该结果可能有助于有效利用奥巴松酮或其衍生物治疗人类结直肠癌。Obacunone 抑制结直肠癌细胞的增殖活性。此外，奥巴康酮诱导结直肠癌细胞G1期和G2期停滞，并抑制细胞周期基因的表达。结论奥巴松酮可通过抑制炎症反应和抑制肿瘤细胞增殖来缓解CRC。该结果可能有助于有效利用奥巴松酮或其衍生物治疗人类结直肠癌。