Center for Herbal Medicine Improvement Research, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea.
Exp Mol Med. 2011 Dec 31;43(12):693-701. doi: 10.3858/emm.2011.43.12.080.
The human colorectal carcinoma-associated GA733 antigen epithelial cell adhesion molecule (EpCAM) was initially described as a cell surface protein selectively expressed in some myeloid cancers. Gangliosides are sialic acid-containing glycosphingolipids involved in inflammation and oncogenesis. We have demonstrated that treatment with anti-EpCAM mAb and RAW264.7 cells significant inhibited the cell growth in SW620 cancer cells, but neither anti-EpCAM mAb nor RAW264.7 cells alone induced cytotoxicity. The relationship between ganglioside expression and the anti- cancer effects of anti-EpCAM mAb and RAW264.7 was investigated by high-performance thin-layer chromatography. The results demonstrated that expression of GM1 and GD1a significantly increased in the ability of anti-EpCAM to inhibit cell growth in SW620 cells. Anti-EpCAM mAb treatment increased the expression of anti-apoptotic proteins such as Bcl-2, but the expression of pro-apoptotic proteins Bax, TNF-α, caspase-3, cleaved caspase-3, and cleaved caspase-8 were unaltered. We observed that anti-EpCAM mAb significantly inhibited the growth of colon tumors, as determined by a decrease in tumor volume and weight. The expression of anti-apoptotic protein was inhibited by treatment with anti-EpCAM mAb, whereas the expression of pro-apoptotic proteins was increased. These results suggest that GD1a and GM1 were closely related to anticancer effects of anti-EpCAM mAb. In light of these results, further clinical investigation should be conducted on anti-EpCAM mAb to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer.
人类结直肠癌相关 GA733 抗原上皮细胞黏附分子（EpCAM）最初被描述为一种在某些髓系癌症中选择性表达的细胞表面蛋白。神经节苷脂是一种含有唾液酸的糖脂，参与炎症和肿瘤发生。我们已经证明，用抗 EpCAM mAb 和 RAW264.7 细胞处理可显著抑制 SW620 癌细胞的细胞生长，但抗 EpCAM mAb 或 RAW264.7 细胞单独处理均不会诱导细胞毒性。通过高效薄层色谱法研究了神经节苷脂表达与抗 EpCAM mAb 和 RAW264.7 的抗癌作用之间的关系。结果表明，GM1 和 GD1a 的表达在抗 EpCAM 抑制 SW620 细胞生长的能力中显著增加。抗 EpCAM mAb 处理增加了抗凋亡蛋白如 Bcl-2 的表达，但促凋亡蛋白 Bax、TNF-α、caspase-3、cleaved caspase-3 和 cleaved caspase-8 的表达没有改变。我们观察到，抗 EpCAM mAb 可显著抑制结肠癌肿瘤的生长，表现为肿瘤体积和重量的减少。抗 EpCAM mAb 处理抑制了抗凋亡蛋白的表达，而促凋亡蛋白的表达增加。这些结果表明，GD1a 和 GM1 与抗 EpCAM mAb 的抗癌作用密切相关。鉴于这些结果，应进一步对抗 EpCAM mAb 进行临床研究，以确定其对人类结肠癌的潜在化学预防和/或治疗效果。
