灵芝三萜化合物的抗肿瘤靶点预测与活性验证(1)
[摘要]研究發现灵芝三萜类化合物具有抗肿瘤活性，但其作用靶点尚不清楚，该试验主要研究灵芝三萜类化合物的抗肿瘤活性并对其可能的作用靶点进行预测。采用Discovery Studio软件的LibDock模块，以灵芝子实体中的26种三萜类化合物作为配体，分别与抗肿瘤作用明确的11个靶点蛋白进行分子对接，获得对接的打分结果，评判配体与靶点蛋白受体结合的亲和力，从而进行灵芝三萜类化合物抗肿瘤的虚拟筛选，探讨可能的作用靶点。同时，MTT实验检测26种灵芝三萜类化合物对5种肿瘤细胞的抑制能力，计算IC50，以此反映化合物的抗肿瘤活性。对接结果表明，对接位置数目大于5，且对接得分高于100，可以作为判断化合物是否具有活性的阈值，据此筛选出8种灵芝三萜类化合物可能具有抗肿瘤活性，其中5个具有多靶点作用的三萜成分。MTT细胞实验显示，灵芝酸Y对肺癌细胞H460显示了一定的抑制活性，IC50为22.4 μmol·L-1，其次是7-oxo-ganoderic acid Z2，IC50为43.1 μmol·L-1。其他三萜类化合物对被测肿瘤细胞株未显示活性或活性很弱。该研究建立的分子对接虚拟筛选方法可用于灵芝抗肿瘤活性成分的初步筛选，通过该方法的筛选，结合MTT细胞毒活性实验结果，发现灵芝酸Y具有抗肿瘤，尤其抗肺癌开发的潜在可能性，7-oxo-ganoderic acid Z2和ganoderon B具有一定的抑制活性，其抗肿瘤作用有待于进一步深入研究，该研究结果可为抗肿瘤药物的研制提供参考。
, 百拇医药
[关键词]灵芝子实体； 三萜类化合物； 抗肿瘤； 分子对接； 虚拟筛选
[Abstract]It has reported that Ganoderma lucidum triterpenoids had anti-tumor activity. However， the anti-tumor target is still unclear. The present study was designed to investigate the anti-tumor activity of G. lucidum triterpenoids on different tumor cells， and predict their potential targets by virtual screening. In this experiment， molecular docking was used to simulate the interactions of 26 triterpenoids isolated from G. lucidum and 11 target proteins by LibDock module of Discovery Studio2016 software， then the anti-tumor targets of triterpenoids were predicted. In addition， the in vitro anti-tumor effects of triterpenoids were evaluated by MTT assay by determining the inhibition of proliferation in 5 tumor cell lines. The docking results showed that the poses were greater than five， and Libdock Scores higher than 100， which can be used to determine whether compounds were activity. Eight triterpenoids might have anti-tumor activity as a result of good docking， five of which had multiple targets. MTT experiments demonstrated that the ganoderic acid Y had a certain inhibitory activity on lung cancer cell H460， with IC50 of 22.4 μmol·L-1， followed by 7-oxo-ganoderic acid Z2， with IC50 of 43.1 μmol·L-1. However， the other triterpenoids had no anti-tumor activity in the detected tumor cell lines. Taking together， molecular docking approach established here can be used for preliminary screening of anti-tumor activity of G.lucidum ingredients. Through this screening method， combined with the MTT assay， we can conclude that ganoderic acid Y had antitumor activity， especially anti-lung cancer， and 7-oxo-ganoderic acid Z2 as well as ganoderon B， to a certain extent， had anti-tumor activity. These findings can provide basis for the development of anti-tumor drugs. However， the anti-tumor mechanisms need to be further studied., 百拇医药(杜国华 王宏旭 闫征 刘莉莹 陈若芸)
, 百拇医药
[关键词]灵芝子实体； 三萜类化合物； 抗肿瘤； 分子对接； 虚拟筛选
[Abstract]It has reported that Ganoderma lucidum triterpenoids had anti-tumor activity. However， the anti-tumor target is still unclear. The present study was designed to investigate the anti-tumor activity of G. lucidum triterpenoids on different tumor cells， and predict their potential targets by virtual screening. In this experiment， molecular docking was used to simulate the interactions of 26 triterpenoids isolated from G. lucidum and 11 target proteins by LibDock module of Discovery Studio2016 software， then the anti-tumor targets of triterpenoids were predicted. In addition， the in vitro anti-tumor effects of triterpenoids were evaluated by MTT assay by determining the inhibition of proliferation in 5 tumor cell lines. The docking results showed that the poses were greater than five， and Libdock Scores higher than 100， which can be used to determine whether compounds were activity. Eight triterpenoids might have anti-tumor activity as a result of good docking， five of which had multiple targets. MTT experiments demonstrated that the ganoderic acid Y had a certain inhibitory activity on lung cancer cell H460， with IC50 of 22.4 μmol·L-1， followed by 7-oxo-ganoderic acid Z2， with IC50 of 43.1 μmol·L-1. However， the other triterpenoids had no anti-tumor activity in the detected tumor cell lines. Taking together， molecular docking approach established here can be used for preliminary screening of anti-tumor activity of G.lucidum ingredients. Through this screening method， combined with the MTT assay， we can conclude that ganoderic acid Y had antitumor activity， especially anti-lung cancer， and 7-oxo-ganoderic acid Z2 as well as ganoderon B， to a certain extent， had anti-tumor activity. These findings can provide basis for the development of anti-tumor drugs. However， the anti-tumor mechanisms need to be further studied., 百拇医药(杜国华 王宏旭 闫征 刘莉莹 陈若芸)