Su Meng, Qin Baoli, Liu Fang, Chen Yuze, Zhang Rui
Department of Internal Medicine.
Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Liaoning, China.
Drug Des Devel Ther. 2017 Nov 23;11:3333-3341. doi: 10.2147/DDDT.S140354. eCollection 2017.
Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide. 5-Fluorouracil (5-Fu) is the most important chemotherapeutic drug used for the treatment of CRC. However, resistance to 5-Fu therapies is a growing concern in CRC clinical practice recently. Andrographolide (Andro) is a main bioactive constituent of the herb , which has various biological effects including anti-inflammation and antitumor activities. In the present study, we investigated the effects of combined Andro with 5-Fu against CRC HCT-116 cells. In vitro studies showed that Andro synergistically enhanced the anti-proliferation effect of 5-Fu on HCT-116 cells due to increased apoptotic cells. Meanwhile, results of the enzyme linked immunosorbent assay indicated that the level of phosphorylated cellular-mesenchymal to epithelial transition factor (p-MET) was decreased by the combination treatment. Further study suggested that Andro promoted the antitumor effect of 5-Fu by down-regulating the level of p-MET. In conclusion, these results confirmed the synergistic antitumor activity of Andro on CRC and provide evidence for possible clinical application of Andro for enhancing the antitumor effect of 5-Fu in CRC treatment.
结直肠癌（CRC）是全球第三大常见恶性肿瘤。5-氟尿嘧啶（5-Fu）是用于治疗CRC的最重要的化疗药物。然而，最近在CRC临床实践中，对5-Fu治疗的耐药性日益受到关注。穿心莲内酯（Andro）是该草药的主要生物活性成分，具有多种生物学效应，包括抗炎和抗肿瘤活性。在本研究中，我们研究了Andro与5-Fu联合对CRC HCT-116细胞的影响。体外研究表明，由于凋亡细胞增加，Andro协同增强了5-Fu对HCT-116细胞的抗增殖作用。同时，酶联免疫吸附测定结果表明，联合治疗降低了磷酸化细胞间充质向上皮转化因子（p-MET）的水平。进一步研究表明，Andro通过下调p-MET水平促进了5-Fu的抗肿瘤作用。总之，这些结果证实了Andro对CRC的协同抗肿瘤活性，并为Andro在CRC治疗中增强5-Fu抗肿瘤作用的可能临床应用提供了证据。
