Abstract: Objective Using molecular docking virtual screening and TCMSP to screen out traditional Chinese medicines and sections that may have anti-lung adenocarcinoma effects, and studying it’s effects against lung adenocarcinoma in vitro. Methods Small molecule compounds of TCSMP database were screened based on Lipinski’s rule of five and ADME were docked with EGFR^{L858R/T790M/C797S} to obtain candidate traditional Chinese medicines or sections against lung adenocarcinoma through the frequency of docking molecules; preliminary validation of anti-lung adenocarcinoma activity and in vitro screening of extract of candidate traditional Chinese medicines or sections against lung adenocarcinoma using MTT method. Further optimization of candidate traditional Chinese medicines or sections against lung adenocarcinoma through differential killing effects of drugs on human lung adenocarcinoma cells NCI-H1975 and human lung fibroblast cells HPF; flow cytometry was used to detect the effects of drugs on apoptosis and mitochondrial membrane potential of NCI-H1975; Western blot was used to detect the effects of drugs on protein expression and phosphorylation of EGFR and its downstream target AKT. Results Through molecular docking results and literature research to screen 8 candidate traditional Chinese medicines (Myristicae Semen, Forsythiae Fructus, Stemonae Radix, Lobeliae Chinensis herba, Curcumae Radix, Piperis Longi Fructus, Polygonati Odorati Rhizoma and Anemarrhenae Rhizoma) and 3 parts of traditional Chinese medicine (total alkaloids of Radix Stemonae, total saponins of Anemarrhenae Rhizoma and total saponins of Gynostemma Pentaphyllum); in vitro experiment studies found that extract of Anemarrhenae Rhizoma and Forsythiae Fructus, total alkaloids of Radix Stemonae and total saponins of Anemarrhenae Rhizoma had strong killing effects on NCI-H1975, with a certain time and dose dependent effect. At the same dose, extract of Forsythiae Fructus and total saponins of Anemarrhenae Rhizoma had weak killing effects on HPF. Further research found that they can decrease mitochondrial membrane potential, induce apoptosis and inhibit the activation of the EGFR-PI3K/AKT signaling pathway of NCI-H1975. Conclusion Based on the specific target of lung adenocarcinoma, the database of traditional Chinese medicines and components can be used to virtually screen anti-lung adenocarcinoma traditional Chinese medicines or sections through molecular docking and other ways, and in vitro experiments were used to detect differential effects of traditional Chinese medicines or sections against lung adenocarcinoma on lung adenocarcinoma cells and normal lung cells, further optimize the screening results, and reveal it’s anti-lung adenocarcinoma mechanism.

Key words: lung adenocarcinoma, EGFR, molecular docking, Forsythiae Fructus, total saponins of Anemarrhenae Rhizoma, mitochondrial membrane potential, cell apoptosis