Zhang Rui, Zhao Jian, Xu Jian, Jiao De-Xin, Wang Jian, Gong Zhi-Qiang, Jia Jian-Hui
Department of Colorectal Surgery, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Department of Radiotherapy, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Oncol Lett. 2017 Oct;14(4):4305-4310. doi: 10.3892/ol.2017.6669. Epub 2017 Jul 26.
Modern pharmacological research has revealed that andrographolide has various functions, including anti-bacterial, anti-inflammatory and anti-viral effects, immunoregulation, treating cardiovascular and cerebrovascular diseases, and prevention and treatment of alcoholic liver injury. The present study investigated whether andrographolide suppresses the proliferation of human colon cancer cell through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB/matrix metalloproteinase-9 (MMP-9) signaling pathway. The MTT assay and lactate dehydrogenase assay were used to evaluate the anticancer effects of andrographolide on cell proliferation and cytotoxicity in human colon cancer SW620 cells. Flow cytometry was used to analyze the anticancer effects of andrographolide on apoptosis by Annexin V-fluorescein isothiocyanate/propidium iodide kit. The effects of andrographolide on the activity of caspase-3/9 were measured using ELISA. Western blot analysis was also used to analyze the protein expression of TLR4, myeloid differentiation primary response gene 88 (MyD88), NF-κB-p65 and MMP-9. In the present study, it was found that andrographolide suppressed the cell proliferation, augmented cytotoxicity, evoked cell apoptosis and activated caspase-3/9 activities in human colon cancer SW620 cells. The results revealed that the anti-proliferation effects of andrographolide on the SW620 cells was associated with the inhibition of TLR4, MyD88, NF-κB-p65 and MMP-9 signaling activation. The results suggest that andrographolide is a promising drug for treatment of human colon cancer via suppression of the TLR4/NF-κB/MMP-9 signaling pathway.
现代药理学研究表明,穿心莲内酯具有多种功能,包括抗菌、抗炎和抗病毒作用、免疫调节、治疗心脑血管疾病以及预防和治疗酒精性肝损伤。本研究调查了穿心莲内酯是否通过Toll样受体4(TLR4)/核因子(NF)-κB/基质金属蛋白酶-9(MMP-9)信号通路抑制人结肠癌细胞的增殖。采用MTT法和乳酸脱氢酶法评估穿心莲内酯对人结肠癌SW620细胞增殖和细胞毒性的抗癌作用。通过Annexin V-异硫氰酸荧光素/碘化丙啶试剂盒,利用流式细胞术分析穿心莲内酯对细胞凋亡的抗癌作用。使用酶联免疫吸附测定法检测穿心莲内酯对caspase-3/9活性的影响。蛋白质印迹分析也用于分析TLR4、髓样分化初级反应基因88(MyD88)、NF-κB-p65和MMP-9的蛋白表达。在本研究中,发现穿心莲内酯抑制人结肠癌SW620细胞的增殖,增强细胞毒性,诱导细胞凋亡并激活caspase-3/9活性。结果显示,穿心莲内酯对SW620细胞的抗增殖作用与抑制TLR4、MyD88、NF-κB-p65和MMP-9信号激活有关。结果表明,穿心莲内酯有望通过抑制TLR4/NF-κB/MMP-9信号通路治疗人类结肠癌。