Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Cancer Sci. 2020 May;111(5):1619-1630. doi: 10.1111/cas.14345. Epub 2020 Mar 16.
Recent studies have shown that MDR could be induced by the high stemness of cancer cells. In a previous study, we found bufalin could reverse MDR and inhibit cancer cell stemness in colorectal cancer, but the relationship between them was unclear. Here we identified overexpressing CD133 increases levels of Akt/nuclear factor-κB signaling mediators and MDR1, while increasing cell chemoresistance. Furthermore, bufalin reverses colorectal cancer MDR by regulating cancer cell stemness through the CD133/nuclear factor-κB/MDR1 pathway in vitro and in vivo. Taken together, our results suggest that bufalin could be developed as a novel 2-pronged drug that targets CD133 and MDR1 to eradicate MDR cells and could ultimately be combined with conventional chemotherapeutic agents to improve treatment outcomes for patients with colorectal cancer.
最近的研究表明，多药耐药性可能是由癌细胞的高干性引起的。在之前的一项研究中，我们发现蟾毒灵可以逆转结直肠癌中的多药耐药性并抑制癌细胞干性，但它们之间的关系尚不清楚。在这里，我们发现过表达 CD133 会增加 Akt/核因子-κB 信号转导介质和 MDR1 的水平，同时增加细胞的化疗耐药性。此外，蟾毒灵通过 CD133/核因子-κB/MDR1 通路在体外和体内逆转结直肠癌的多药耐药性，调节癌细胞干性。综上所述，我们的研究结果表明，蟾毒灵可以开发为一种新型的双靶点药物，靶向 CD133 和 MDR1，以消除多药耐药细胞，最终可以与传统化疗药物联合使用，改善结直肠癌患者的治疗效果。
