COROSOLIC ACID INHIBITS THE GROWTH OF HUMAN NON-SMALL-CELL LUNG CANCER A549 CELLS BY REGULATING THE VEGF/VEGFR2 SIGNALLING PATHWAY

Objective: To investigate the effects of comsolic acid (CA) on the lung cancer cell cycle, apoptosis, the VEGF/VEGFR2 signalling pathway and drug targeting. Methods: A549, a lung cancer cell line, was routine cultured in vitro. The effects of comsolic acid on the cell cycle, apoptosis, and the expression of the proteins and mRNA related to the VEGF/VEGFR2 signalling pathway in A549 cells were detected by flow cytometry. Twenty-four BALB/c-bearing nude mice with subcutaneous transplanted tumours of up to 200 mm3 were randomly divided into four groups (high, medium, and low CA dose groups and a solvent control group) according to tumour volume, with 6 mice per group. The drug was given by intragastric administration once per day for 21 consecutive days, and the tumour volume was measured every 3 days. At 24 h after the last administration, the animals were euthanized with CO2 gas and the solid tumour was removed. The tumours were photographed and weighed according to their group and number, and the relative tumour proliferation rate and tumour growth inhibition rate were calculated. In addition, 12 nude mice bearing subcutaneously successful BALB/c tumours were randomly divided into a corosolic acid group and a solvent control group according to tumour volume, with 6 mice per group. The drug was given by intragastric administration once; 24 h after administration, the animals were euthanized with CO2 gas and the solid tumour was removed. The fluorescence value of the solid tumour was detected using a small animal in vivo imaging system. Results: Corosolic acid can induce apoptosis of A549 cells and block the cell cycle in the G(0)/G(1) phase in vitro, decrease the expression of VEGF/VEGFR2 signalling-pathway-related proteins and mRNA, effectively inhibit the growth of solid tumours in tumour-bearing animals, and exhibit obvious aggregation in the solid tumour site. Conclusion: Corosolic acid can inhibit lung cancer by regulating the VEGF/VEGFR2 signalling pathway.