PO.PR02.01 · 预防研究
Rheum webbianum 通过调节 Wnt/beta-catenin 和 TGF-beta 信号通路对结直肠癌的化学预防作用：来自体外和体内研究的见解
Chemopreventive effects of Rheum webbianum against colorectal cancer via modulation of Wnt/beta-catenin and TGF-beta signaling: Insights from in-vitro and in-vivo studies
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摘要 Abstract
中文摘要
背景：结直肠癌（CRC）是全球最常见的恶性肿瘤之一，很大程度上受生活方式和环境因素影响。寻找安全的天然化学预防药物仍是一项关键研究优先事项。Rheum webbianum Royle（RW）是一种具有显著民族药理学意义的喜马拉雅药用植物，在既往研究中已显示出有前景的抗癌活性。基于我们早期证实其对 DMH 诱导的结肠癌变具有保护作用的研究结果，本研究进一步探讨 RW 乙醇提取物的抗癌潜力，重点关注其对分子通路和直肠组织形态的影响。
方法：采用体外和体内两种方法评估 RW 乙醇提取物。在 HT-29 结直肠腺癌细胞中，采用细胞毒性实验和划痕愈合实验检测抗增殖和抗迁移作用。通过 Western blot 分析 beta-catenin 和 TGF-beta1 表达的变化。体内评估采用 1,2-二甲基肼（DMH）诱导的 CRC 大鼠模型，研究直肠组织中的分子调控和组织病理学改变。
结果：体外实验中，RW 提取物以剂量和时间依赖的方式显著降低 HT-29 细胞活力，在 200 µg/mL 时抑制率约达 80%，并显著削弱癌细胞迁移能力。体内实验中，RW 处理下调 beta-catenin 和 TGF-beta1 表达，表明其抑制了致癌和促转移信号。组织病理学：显微镜检查显示，与仅 DMH 处理组大鼠相比，RW 处理组的直肠组织结构显著恢复。RW 处理动物的上皮破坏、充血、炎性浸润、隐窝脓肿和异型增生减少，而仅 DMH 处理组则表现出严重的黏膜损伤、腺体排列不规则以及伴有隐窝脓肿和异型增生的广泛炎性病变。这些发现提示 RW 提取物在预防 DMH 诱导的结直肠组织退行性变方面具有保护效力。
结论：Rheum webbianum 乙醇提取物通过抑制肿瘤细胞增殖、迁移以及 Wnt/beta-catenin 和 TGF-beta 信号通路的异常激活，同时恢复直肠组织完整性，展现出对结直肠癌变的强大化学预防潜力。这些结果支持 RW 作为结直肠癌预防和整合治疗开发的有前景的天然候选药物。
查看英文原文 English abstract
Background: Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, largely influenced by lifestyle and environmental factors. The search for safe, natural chemopreventive agents remains a key research priority. Rheum webbianum Royle (RW), a Himalayan medicinal plant with notable ethnopharmacological significance, has shown promising anticarcinogenic activity in prior studies. Building on our earlier findings demonstrating its protective effects against DMH-induced colon carcinogenesis, the present study further explores the anticancer potential of RW ethanolic extract, focusing on its influence on molecular pathways and rectal tissue morphology.
Methods: The ethanolic extract of RW was assessed using both in-vitro and in-vivo approaches. In HT-29 colorectal adenocarcinoma cells, cytotoxicity and wound-healing assays were used to examine antiproliferative and antimigratory effects. Western blotting analyzed alterations in beta-catenin and TGF-beta1 expression. In-vivo evaluation was performed using a 1,2-dimethylhydrazine (DMH)-induced CRC rat model to investigate molecular modulation and histopathological alterations in rectal tissues.
Results: In-vitro , RW extract markedly reduced HT-29 cell viability in a dose- and time-dependent manner, reaching approximately 80% inhibition at 200 µg/mL, and significantly impaired cancer cell migration. In-vivo , RW treatment downregulated beta-catenin and TGF-beta1 expression, indicating inhibition of oncogenic and pro-metastatic signaling.Histopathology: Microscopic examination revealed marked restoration of rectal tissue architecture in RW-treated groups compared to DMH-only rats. RW-treated animals showed reduced epithelial disruption, congestion, inflammatory infiltration, crypt abscesses, and dysplasia, while DMH-only groups exhibited severe mucosal damage, irregular glandular organization, and extensive inflammatory lesions with crypt abscesses and dysplasia. These findings suggest the protective efficacy of RW extracts in preventing DMH-induced colorectal tissue degeneration.
Conclusion: The ethanolic extract of Rheum webbianum demonstrates strong chemopreventive potential against colorectal carcinogenesis by suppressing tumor cell proliferation, migration, and aberrant activation of Wnt/beta-catenin and TGF-beta signaling pathways, along with restoring rectal tissue integrity. These outcomes support RW as a promising natural candidate for colorectal cancer prevention and integrative therapeutic development.
利益披露 Disclosure
U. M. Khaja, None..
R. Singh, None..
S. A. Ganie, None.