Mechanism of drug-containing serum of Buzhong Yiqi Decoction in inhibiting the activity and vasculogenic mimicry of lung cancer cells

Objective To investigate the effects and mechanisms of drug-containing serum of Buzhong Yiqi Decoction on the activity and vasculogenic mimicry (VM) of lung cancer cells.

Methods Drug-containing serum of Buzhong Yiqi Decoction with low-dose (BZ-L group), medium-dose (BZ-M group), and high-dose (BZ-H group) were prepared through gastric lavage in SD rats to intervene lung cancer cells. CCK-8 assay, Edu cell proliferation assay, cell clone formation assay, cell scratch assay, and Transwell assay were used to detect the effects of Buzhong Yiqi Decoction on the proliferation and migration of lung cancer A549 and HCC827 cells. Flow cytometry was employed to detect the impacts of Buzhong Yiqi Decoction on lung cancer cell apoptosis and cell cycle, and VM experiments in vitro were conducted to assess the effect of Buzhong Yiqi Decoction on angiogenesis in lung cancer cells. Differentially expressed genes between control cells and drug-intervened cells were detected by RNA-seq sequencing. Subcutaneous xenografts in mice were established to evaluate the inhibitory effect of gavage therapy of Buzhong Yiqi Decoction on the growth of lung cancer cells in vivo.

Results Buzhong Yiqi Decoction inhibited the viability and proliferative activity of A549 and HCC827 cells in a dose-dependent manner, promoted lung cancer cell apoptosis in a dose-dependent manner, and induced G₂/M phase arrest. The migration ability of A549 and HCC827 cells was significantly reduced after Buzhong Yiqi Decoction intervention. As the concentration of Buzhong Yiqi Decoction increased, the VM of A549 and HCC827 cells gradually decreased. Compared with control cells, 765 differentially expressed genes were identified in the Buzhong Yiqi Decoction group, with significant downregulation of p-JNK and p-ERK1/2 gene expression. Western blot analysis revealed that the phosphorylation level of the JNK/ERK1/2 signaling pathway in A549 and HCC827 cells was gradually inhibited with increasing concentrations of Buzhong Yiqi Decoction. Buzhong Yiqi Decoction significantly reduced the volume and mass of mouse tumors, increased the apoptosis rate in tumor tissues, decreased the expression of p-JNK, p-ERK1, and p-ERK2, and increased the expression of E-cadherin in tumor tissues.

Conclusion Buzhong Yiqi Decoction may inhibit the activity and angiogenesis of lung cancer cells by suppressing the activity of the JNK/ERK1/2 signaling pathway.