Study on the Mechanism of Zhoushi Gujin Xiaoliu Tang Against Human Lung Adenocarcinoma A549 Cells Based on JAK2/STAT3/VEGF Pathway

OBJECTIVE  To investigate the effect and mechanism of Zhoushi Gujin Xiaoliu Tang (ZSGJXLT) on proliferation, apoptosis and angiogenesis of human lung adenocarcinoma A549 cells.METHODS   The activity of A549 cells was detected by CCK-8.The apoptosis of A549 cells was observed by the Annexin-V-FITC/PI flow cytometry. The cell angiogenesis ability was evaluated by human umbilical vein endothelial cell (HUVEC) angiogenesis assay in vitro. The expression of Bcl - 2, Bax, VEGF, JAK2, p-JAK2, STAT3 and p-STAT3 proteins were detected by Western blot. The A549 lung cancer xenograft model was constructed and treated with ZSGJXLT, which was divided into different concentrations. After 21 days, the mice were sacrificed to weigh the tumors and the tumor inhibitory rate was calculated.RESULTS   The proliferation of A549 were apparently inhibited by ZSGJXLT in a concentration and time-dependent manner (P < 0.01). ZSGJXLT also induced A549 cell apoptosis significantly in a concentration-dependent manner (P < 0.05, P < 0.01). In addition, the number of annular vascular structure was decreased by ZSGJXLT (P < 0.01). The result of Western blot showed that ZSGJXLT promoted the up-regulation of Bax/Bcl-2 (P < 0.05, P < 0.01) and inhibited the expression of VEGF, p-STAT3/STAT3 and p-JAK2/JAK2 (P < 0.05). In vivo, ZSGJXLT (0.25, 1, 4 g/kg) also statically inhibited the growth of lung cancer xenograft in nude mice model in a concentration-dependent manner (P < 0.05, P < 0.01), with tumor inhibitory rates of 21.66%, 35.52% and 48.24%, respectively.CONCLUSION  ZSGJXLT inhibits the activation of JAK2/STAT3/VEGF signaling pathway, thereby inhibiting tumor cell proliferation, promoting tumor cell apoptosis, anti-tumor angiogenesis and other ways to play anti-tumor effects. This research provides experimental evidence of ZSGJXLT for lung cancer.