[Anti-gastric cancer effects of Z Ajoene and its molecular mechanisms]

Objective: To investigate the effects of Z Ajoene on gastric cancer cell MGC-803 and its molecular mechanisms. Methods: The gastric cancer cells MGC-803 were treated with 0, 1, 5, 25 and 125 μmol/L Z Ajoene for 24 h, 48 h and 72 h, each with 3 replicate wells. The proliferation activity of MGC-803 cells was analyzed by MTS method, mitochondrial membrane potential was analyzed after JC-1 staining, nuclear type was observed after Hoechst 33342 staining, cytotoxicity was detected by LDH release method, and the apoptosis level and cell cycle were analyzed with flow cytometry. RT-qPCR and Western blot methods were used to evaluate the expression levels of P53, Caspase-3, RAS, ERK, BCL-2, AKT, mTOR and PI3K genes. At the same time, 4-week-old male BALB/C mice were randomly divided into 5 groups, 20 per group, and were subcutaneously inoculated with gastric cancer cell MGC-803 in the groin. Two days later, each group was injected with Z Ajoene at the doses of 0, 1, 5, 25 and 125 μmol/L, 0.1 ml/time, and was injected every other day. On the 20th day of the first injection of tumor cells, 10 mice in each group were killed, the tumor tissues were taken out and weighed. The survival period of the remaining mice was recorded and the effects of Z Ajoene on the growth and survival period of gastric cancer in tumor-bearing mice were observed. Results: After Z Ajoene treatment, the proliferation activity of MGC-803 cells was significantly inhibited and the apoptosis rate was significantly increased(P＜0.01). The transcription and expression levels of p53, Caspase-3 and BAX genes were significantly increased, while the transcription and expression levels of RAS, ERK1, BCL-2, AKT, mTOR and PI3K genes were decreased markedly(P＜0.01). The tumor inhibition experiments showed that the growth of the tumor could be inhibited and the survival time of the tumor-bearing animals could be greatly prolonged after Z Ajoene treatment(P＜0.01). Conclusion: Z Ajoene has therapeutic effects on gastric cancer, can inhibit the proliferation of gastric cancer cells and induce them apoptosis by regulating the expression of PI3K-AKT-mTOR and RAS-RAF-MEK-ERK signal pathways.