Zou Yi-Feng, Rong Yu-Ming, Chen Ze-Xian, Shen Zhi-Hong, Chen Xi, Tan Ying-Xin, Weng Jing-Rong, Huang Xiao-Ming, Lin Xu-Tao
Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Onco Targets Ther. 2020 Aug 26;13:8691-8704. doi: 10.2147/OTT.S253598. eCollection 2020.
Huaier extract has been a part of traditional Chinese medicine (TCM) for roughly 1600 years and may serve as a potential anti-cancer drug as it is associated with good efficacy and low toxicity. Individuals with inflammatory bowel disease (IBD) are at a higher chance of being diagnosed with colorectal cancer (CRC) and as Huaier extract may potentially influence tumorigenesis, we set out to determine the effect of Huaier extract on colitis-associated CRC.
The CRC mouse model, established through azoxymethane (AOM) and dextran sulfate sodium (DSS), was administered Huaier extract. Weight loss, colon length, tumor number and tumor size were evaluated macroscopically. Pro-inflammatory cytokine expression and STAT3 phosphorylation were assessed in the colon using ELISA, Western blot and/or immunohistochemistry.
Huaier extract improved the severity of colitis-associated tumorigenesis compared with control group, with attenuated weight loss and longer colons. Tumor number, size and load were drastically decreased in mice treated with Huaier. Histological assessment suggested that Huaier could decrease histological injury of the colon tissue. Additionally, Huaier extract treatment led to reduced pro-inflammatory cytokine levels (TNF-α, IL-6, IFN-γ and IL-1β) and a decrease of STAT3 phosphorylation in colon tissue. Additionally, present findings demonstrated that Huaier extract inhibited cell proliferation and induced apoptosis in CRC cells HCT116 and HCT8. The migration and invasion of CRC cells were markedly inhibited upon exposure to Huaier treatment. The apoptosis-associated protein levels (P53, Bax, Bcl-2, pro-caspase-3 and cleavage caspase-3) showed significant differences after the administration of Huaier extract in HCT116 and HCT8 cells. In vivo, the administration of Huaier extract to mice inhibited tumor growth and yielded a similar profile of apoptotic proteins expression p53, Bcl-2, pro-caspase-3 and cleaved caspase-3 while no significant differences in Bax were observed. Moreover, the ratio of TUNEL-positive/apoptotic cells was markedly increased in the Huaier-treated mice.
Huaier extract may reduce the IBD-associated tumor development by suppressing pro-inflammatory cytokine levels and STAT3 stimulation.
槐耳提取物作为中药的一部分已有约1600年历史，因其疗效好、毒性低，可能成为一种潜在的抗癌药物。炎症性肠病（IBD）患者患结直肠癌（CRC）的几率更高，由于槐耳提取物可能会影响肿瘤发生，我们着手确定槐耳提取物对结肠炎相关结直肠癌的影响。
通过氧化偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）建立CRC小鼠模型，并给予槐耳提取物。宏观评估体重减轻、结肠长度、肿瘤数量和肿瘤大小。使用酶联免疫吸附测定（ELISA）、蛋白质免疫印迹法和/或免疫组织化学评估结肠中促炎细胞因子的表达和信号转导及转录激活因子3（STAT3）磷酸化。
与对照组相比，槐耳提取物改善了结肠炎相关肿瘤发生的严重程度，体重减轻减轻，结肠更长。用槐耳治疗的小鼠肿瘤数量、大小和负荷显著降低。组织学评估表明，槐耳可减轻结肠组织的组织学损伤。此外，槐耳提取物治疗导致结肠组织中促炎细胞因子水平（肿瘤坏死因子-α、白细胞介素-6、干扰素-γ和白细胞介素-1β）降低以及STAT3磷酸化减少。此外，目前的研究结果表明，槐耳提取物抑制CRC细胞HCT116和HCT8的细胞增殖并诱导其凋亡。暴露于槐耳治疗后，CRC细胞的迁移和侵袭明显受到抑制。在HCT116和HCT8细胞中给予槐耳提取物后，凋亡相关蛋白水平（P53、Bax、Bcl-2、前半胱天冬酶-3和裂解的半胱天冬酶-3）显示出显著差异。在体内，给小鼠施用槐耳提取物可抑制肿瘤生长，并产生与凋亡蛋白p53、Bcl-2、前半胱天冬酶-3和裂解的半胱天冬酶-3表达相似的情况，而Bax未观察到显著差异。此外，在槐耳治疗的小鼠中，TUNEL阳性/凋亡细胞的比例显著增加。
槐耳提取物可能通过抑制促炎细胞因子水平和STAT3激活来减少IBD相关的肿瘤发展。
