Research on the mechanism of Hedyotis diffusa extract inhibiting tumor angiogenesis and inducing apoptosis in gastric cancer-bearing mice by regulating the PGK1-VEGF axis

Objective To investigate the effects and mechanisms of Hedyotis diffusa (HDE) on tumor growth, tissue angiogenesis and apoptosis in MFC gastric cancer tumor-bearing mice.

Methods A tumor model of MFC gastric cancer cells was established, and the model mice were randomly divided into the model group, low-dose (50 mg/kg) HDE group, high-dose (100 mg/kg) HDE group and high-dose HDE + phosphoglycerate kinase 1 (PGK1) agonist (terazosin 0.3 mg/kg) group, with 6 mice in each group. The four group were given the corresponding drugs or 0.9% sodium chloride solution by gavage or intraperitoneal injection once a day for 14 days. The tumor inhibition rate and organ coefficient were calculated. HE staining was used to observe the pathological morphological changes of the tumor. Immunohistochemical staining was used to detect the protein expressions of Ki67 and proliferating cell nucleus (PCNA) in tumor tissues. Immunofluorescence staining was used to detect the expression of CD31 protein in tumor tissues. The apoptotic level of tumor tissue cells was detected by TUNEL staining. The protein expressions of Bax, Bcl-2, PGK1 and vascular endothelial growth factor (VEGF) were detected by Western blotting.

Results Compared with the model group, the tumor tissues of gastric cancer tumor-bearing mice in the low-dose and high-dose HDE groups showed vacuolar degeneration, cell density decrease, and tumor volume, mass, Ki67, PCNA, microvessel density, Bcl-2, PGK1 and VEGF protein levels decrase (P ＜ 0.05), while the tumor inhibition rate and Bax protein level increased, and the differences were all statistically significant (P ＜ 0.05). The tumor-suppressing effect of HDE on gastric cancer-bearing mice was dose-dependent, and the differences were statistically significant (P ＜ 0.05). Moreover, PGK1 agonists could reverse the tumor-suppressing effect of HDE, and the differences were also statistically significant (P ＜ 0.05).

Conclusions HDE can inhibit tumor tissue growth and angiogenesis in mice with gastric cancer tumors, and promote apoptosis. The mechanism may be related to the down-regulation of PGK1-VEGF axis.