Molecular mechanism of the treatment of lung adenocarcinoma by Hedyotis Diffusa: an integrative study with real-world clinical data and experimental validation

Abstract

BackgroundWith a variety of active ingredients, Hedyotis Diffusa (H. diffusa) can treat a variety of tumors. The purpose of our study is based on real-world data and experimental level, to double demonstrate the efficacy and possible molecular mechanism of H. diffusa in the treatment of lung adenocarcinom (LUAD).MethodsPhenotype-genotype and herbal-target associations were extracted from the SymMap database. Disease-gene associations were extracted from the MalaCards database. A molecular network-based correlation analysis was further conducted on the collection of genes associated with TCM and the collection of genes associated with diseases and symptoms. Then, the network separation SAB metrics were applied to evaluate the network proximity relationship between TCM and symptoms. Finally, cell apoptosis experiment, Western blot, and Real-time PCR were used for biological experimental level validation analysis.ResultsIncluded in the study were 85,437 electronic medical records (318 patients with LUAD). The proportion of prescriptions containing H. diffusa in the LUAD group was much higher than that in the non-LUAD group (p < 0.005). We counted the symptom relief of patients in the group and the group without the use of H. diffusa: except for symptoms such as fatigue, palpitations, and dizziness, the improvement rate of symptoms in the user group was higher than that in the non-use group. We selected the five most frequently occurring symptoms in the use group, namely, cough, expectoration, fatigue, chest tightness and wheezing. We combined the above five symptom genes into one group. The overlapping genes obtained were CTNNB1, STAT3, CASP8, and APC. The selection of CTNNB1 target for biological experiments showed that the proliferation rate of LUAD A549 cells in the drug intervention group was significantly lower than that in the control group, and it was concentration-dependent. H. diffusa can promote the apoptosis of A549 cells, and the apoptosis rate of the high-concentration drug group is significantly higher than that of the low-concentration drug group. The transcription and expression level of CTNNB1 gene in the drug intervention group were significantly decreased.ConclusionH. diffusa inhibits the proliferation and promotes apoptosis of LUAD A549 cells, which may be related to the fact that H. diffusa can regulate the expression of CTNNB1.