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Modified citrus pectin inhibited bladder tumor growth through downregulation of galectin-3.
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2018-Dec-01 , DOI: 10.1038/s41401-018-0004-z
Tian Fang 1 , Dan-Dan Liu 2, 3 , He-Ming Ning 2, 3, 4 , Dan Liu 5 , Jing-Ya Sun 2 , Xiao-Jing Huang 5 , Yu Dong 2, 6 , Mei-Yu Geng 2, 3, 4 , Shi-Feng Yun 1 , Jun Yan 5, 7 , Rui-Min Huang 2, 3
Affiliation  

Modified citrus pectin (MCP) is a carbohydrate enriched complex, which has been implicated in cancer treatment and prevention. However, the effects of MCP on urinary bladder cancer (UBC) are unknown. In this study, MCP was first tested in T24 and J82 human UBC cells and showed the inhibition of cell viability by the sulforhodamine B (SRB) assay. The MCP-treated UBC cells exhibited G2/M phase arrest with the decrease of Cyclin B1 and phosphorylated Cdc2. Caspase-3 was also activated, leading to the cleavage of Caspase-3 and PARP. We further explored the possible molecular mechanisms upon MCP treatment in UBC cells. Reduction of galectin-3 was observed and followed with the inactivation of Akt signaling pathway. Of note, galectin-3 knockdown by RNA interference recapitulated the MCP-mediated anti-proliferation, cell cycle arrest and apoptosis. Moreover, oral administration of MCP to the T24 xenograft-bearing nude mice inhibited the tumor growth significantly (P < 0.05). Quantification analysis of immunohistochemistry staining for Ki67 and cleaved Caspase-3 confirmed the decrease of proliferation index (P < 0.05) and the increase of apoptosis index (P < 0.01) in 700 mg/kg MCP-fed UBC xenografts. Using the information from TCGA database, we revealed that the overexpression of galectin-3 was associated with high tumor grade with lymph node metastasis, poor overall survival in UBC patients. Considering the remarkable inhibitory effects of MCP on UBC cell proliferation and survival in vitro and in vivo mainly through galectin-3, which is upregulated in UBCs, MCP may become an attractive agent, as a natural dietary fiber, for prevention and therapy of UBCs.

中文翻译:

修饰的柑橘果胶通过下调半乳糖凝集素 3 抑制膀胱肿瘤的生长。

改性柑橘果胶 (MCP) 是一种富含碳水化合物的复合物,与癌症的治疗和预防有关。然而,MCP 对膀胱癌 (UBC) 的影响尚不清楚。在这项研究中,MCP 首先在 T24 和 J82 人 UBC 细胞中进行了测试,并通过磺胺罗丹明 B (SRB) 测定显示了对细胞活力的抑制作用。MCP处理的UBC细胞随着Cyclin B1和磷酸化Cdc2的减少而表现出G 2 /M期停滞。Caspase-3 也被激活,导致 Caspase-3 和 PARP 裂解。我们进一步探讨了 MCP 治疗 UBC 细胞的可能分子机制。观察到 galectin-3 减少,随后 Akt 信号通路失活。值得注意的是,通过 RNA 干扰敲低半乳糖凝集素 3 再现了 MCP 介导的抗增殖、细胞周期停滞和细胞凋亡。此外,口服MCP对T24荷瘤裸鼠的肿瘤生长具有显着抑制作用(P < 0.05)。Ki67 和裂解的 Caspase-3 免疫组织化学染色的定量分析证实,700 mg/kg MCP 喂养的 UBC 异种移植物中增殖指数降低(P < 0.05),凋亡指数增加(P < 0.01)。利用TCGA数据库的信息,我们发现galectin-3的过度表达与UBC患者的肿瘤分级高、淋巴结转移、总生存率低有关。考虑到MCP主要通过UBC中上调的galectin-3对体外和体内UBC细胞增殖和存活具有显着的抑制作用,MCP作为天然膳食纤维可能成为预防和治疗UBC的有吸引力的药物。
更新日期:2018-05-16
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