Kwak Dong Hoon, Moussavou Ghislain, Lee Ju Hyoung, Heo Sung Youn, Ko Kisung, Hwang Kyung-A, Jekal Seung-Joo, Choo Young-Kug
Institute of Glycoscience, Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
Department of Biological Science, College of Natural Sciences, Institute of Biotechnology Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
Int J Mol Sci. 2014 Nov 14;15(11):21105-19. doi: 10.3390/ijms151121105.
We have generated the transgenic Tabaco plants expressing multiple monoclonal antibody (mAb) CO7-1A × BR55 by cross-pollinating with mAb CO17-1A and mAb BR55. We have demonstrated the anti-cancer effect of plant-derived multiple mAb CO17-1A × BR55. We find that co-treatment of colorectal mAbs (anti-epithelial cellular adhesion molecule (EpCAM), plant-derived monoclonal antibody (mAb(P)) CO17-1A and mAb(P) CO17-1A × BR55) with RAW264.7 cells significantly inhibited the cell growth in SW620 cancer cells. In particular, multi mAb(P) CO17-1A × BR55 significantly and efficiently suppressed the growth of SW620 cancer cells compared to another mAbs. Apoptotic death-positive cells were significantly increased in the mAb(P) CO17-1A × BR55-treated. The mAb(P) CO17-1A × BR55 treatment significantly decreased the expression of B-Cell lymphoma-2 (BCl-2), but the expression of Bcl-2-associated X protein (Bax), and cleaved caspase-3 were markedly increased. In vivo, the mAb(P) CO17-1A × BR55 significantly and efficiently inhibited the growth of colon tumors compared to another mAbs. The apoptotic cell death and inhibition of pro-apoptotic proteins expression were highest by treatment with mAb(P) CO17-1A × BR55. In addition, the mAb(P) CO17-1A × BR55 significantly inhibited the extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation in cancer cells and tumors. Therefore, this study results suggest that multiple mAb(P) CO17-1A × BR55 has a significant effect on apoptosis-mediated anticancer by suppression of ERK1/2 phosphorylation in colon cancer compared to another mAbs. In light of these results, further clinical investigation should be conducted on mAb(P) CO17-1A × BR55 to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer.
我们通过将单克隆抗体(mAb)CO17-1A与mAb BR55进行异花授粉,培育出了表达多种单克隆抗体CO7-1A×BR55的转基因烟草植株。我们已经证明了植物源多种单克隆抗体CO17-1A×BR55的抗癌作用。我们发现,将结肠直肠癌单克隆抗体(抗上皮细胞黏附分子(EpCAM)、植物源单克隆抗体(mAb(P))CO17-1A和mAb(P))CO17-1A×BR55)与RAW264.7细胞共同处理,可显著抑制SW620癌细胞的生长。特别是,与其他单克隆抗体相比,多种mAb(P) CO17-1A×BR55显著且有效地抑制了SW620癌细胞的生长。在经mAb(P) CO17-1A×BR55处理的细胞中,凋亡死亡阳性细胞显著增加。mAb(P) CO17-1A×BR55处理显著降低了B细胞淋巴瘤-2(BCl-2)的表达,但Bcl-2相关X蛋白(Bax)和裂解的半胱天冬酶-3的表达明显增加。在体内,与其他单克隆抗体相比,mAb(P) CO17-1A×BR55显著且有效地抑制了结肠肿瘤的生长。经mAb(P) CO17-1A×BR55处理后,凋亡细胞死亡和促凋亡蛋白表达的抑制作用最为明显。此外,mAb(P) CO17-1A×BR55显著抑制了癌细胞和肿瘤中细胞外信号调节激酶1和2(ERK1/2)的磷酸化。因此,本研究结果表明,与其他单克隆抗体相比,多种mAb(P) CO17-1A×BR55通过抑制结肠癌中ERK1/2的磷酸化,对凋亡介导的抗癌作用具有显著影响。鉴于这些结果,应对mAb(P) CO17-1A×BR55进行进一步的临床研究,以确定其对人类结肠癌可能的化学预防和/或治疗效果。