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来自茄病镰刀菌的促有丝分裂凝集素可阻止人结肠上皮癌细胞生长、抑制转移并诱导其凋亡。

A mitogenic lectin from Rhizoctonia bataticola arrests growth, inhibits metastasis, and induces apoptosis in human colon epithelial cancer cells.

机构信息

Department of Studies in Biochemistry, Karnatak University, Dharwad, Karnataka, India.

出版信息

J Cell Biochem. 2018 Jul;119(7):5632-5645. doi: 10.1002/jcb.26740. Epub 2018 Mar 14.

Abstract

The correlation between colorectal cancer (CRC) progression and altered expression of N-glycans can be considered in search for new biomarkers and anticancer agents to control CRC. Earlier N-glycan specific mitogenic lectin from Rhizoctonia bataticola (RBL) has been reported which has growth inhibitory and apoptotic effect on human ovarian and leukemic cells, but mitogenic effect on normal PBMCs revealing its clinical potential. Here, we report the effect of RBL on human colon cancer HT 29, SW480, and SW620 cell growth and its differential binding to human normal colon and cancer tissues. RBL has strong binding to both primary and metastatic colon cancer cells with MFI of 403, 404, and 192, respectively for HT 29, SW480, and SW620 cells. RBL shows dose and time dependent growth inhibitory effect with IC of 5, 6.4, and 6.8 µg/mL, respectively for HT 29, SW480, and SW620 cells. RBL inhibited the clonogenicity of colon carcinoma cells. RBL arrests metastatic SW620 cell growth at S phase, increased hypodiploid population by 6.1%, 14.3%, and 23.2%, respectively at 12, 24, and 36 h. Further, RBL induces SW620 cell apoptosis in time dependent manner, showed increased release of ROS and nuclear degradation compared to lectin untreated control. Adhesion, wound healing, invasion, and migration assays demonstrated anti-metastasis effect of RBL in SW620 cells apart from its growth inhibitory effect. Anti angiogenic effect of RBL was demonstrated by CAM assay. All these results show the promising potential of RBL both as diagnostic and therapeutic agent.

摘要

结直肠癌(CRC)进展与 N-糖基化改变表达之间的相关性,可以作为寻找新的生物标志物和抗癌药物来控制 CRC 的研究方向。此前曾报道过 Rhizoctonia bataticola(RBL)中的一种 N-糖基化特异性有丝分裂凝集素,它对人卵巢和白血病细胞具有生长抑制和凋亡作用,但对正常 PBMC 具有有丝分裂作用,显示出其临床潜力。在这里,我们报告了 RBL 对人结肠癌细胞 HT 29、SW480 和 SW620 生长的影响及其与人正常结肠和癌症组织的差异结合。RBL 与人结肠癌细胞的原发性和转移性均具有很强的结合能力,对 HT 29、SW480 和 SW620 细胞的平均荧光强度(MFI)分别为 403、404 和 192。RBL 表现出剂量和时间依赖性的生长抑制作用,IC 分别为 HT 29、SW480 和 SW620 细胞的 5、6.4 和 6.8μg/mL。RBL 抑制结肠癌细胞的集落形成能力。RBL 将转移性 SW620 细胞的生长阻滞在 S 期,分别在 12、24 和 36 h 时将亚二倍体群体增加了 6.1%、14.3%和 23.2%。此外,RBL 以时间依赖性方式诱导 SW620 细胞凋亡,与未经凝集素处理的对照相比,显示出 ROS 释放和核降解增加。黏附、划痕愈合、侵袭和迁移实验表明,除了生长抑制作用外,RBL 还具有抗转移作用。CAM 实验证明了 RBL 的抗血管生成作用。所有这些结果表明,RBL 具有作为诊断和治疗剂的巨大潜力。

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