Study on Inhibitory Effect and Mechanism of Myricanol 5-Fluorobenzyloxy Ether on Proliferation of Human Lung Adenocarcinoma Cells A549-Homo BIRC5 in Vivo

OBJECTIVE To investigate the inhibitory effect and mechanism of myricanol 5-fluorobenzyloxy ether(5FEM) on the proliferation of human lung adenocarcinoma A549-Homo BIRC5 in vivo.METHODS The model of A549-Homo BIRC5 xenograft tumors in nude mice was constructed and randomly divided into model group, solvent(polyethylene glycol 400, 2.5 mL·kg^-1) group and 5FEM low, medium, and high dose(20, 40, 80 mg·kg^-1, respectively) groups, with 8 mice in each group. Each group received daily intraperitoneal injection for 5 weeks, and the tumor volume was measured weekly to draw the tumor growth curve, and the nude mice were sacrificed after the experiment ended, solid tumors were harvested and weighed. The apoptosis of tumor tissue was analysed by TUNEL-staining. The mRNA expression level of Caspase-9, PARP, Bax, Bcl-2 and Survivin in tumor tissues were measured by RT-qPCR; ELISA assay was used to detect the protein levels of Caspase-9, Survivin and PARP in tumor tissues. Immunohistochemistry was adopted to detect the levels of Survivin, Caspase-9, Cleaved caspase-9, PARP and Cleaved PARP proteins in tumor tissues. RESULTS Compared with the model group, 5FEM(20, 40, 80 mg·kg^-1) could significantly reduce the volume and weight of the xenograft tumors in a dose-dependent manner. TUNEL staining showed that the apoptosis of tumor cells after 5FEM intervention was significantly higher than that in model group. RT-qPCR showed that 5FEM(20, 40, 80 mg·kg^-1) could significantly increase the mRNA expression of Caspase-9 and Bax, and decrease the mRNA expression of Bcl-2, PARP and Survivin in tumor tissues. ELISA results showed that 5FEM(40, 80 mg·kg^-1) could significantly increase the expression of Caspase-9 protein in tumor tissues, and significantly decrease the expression of PARP and Survivin protein in tumor tissues. Immunohistochemical results showed that the expressions of Caspase-9, Cleaved caspase-9 and Cleaved PARP protein in tumor tissues were significantly increased after 5FEM(80 mg·kg^-1) treatment, while the expression of PARP and Survivin protein were inhibited in different degrees. CONCLUSION 5FEM can down-regulate the expression of Survivin, promote the activation of Caspase-9 and PARP, induce the apoptosis of tumor cells, and inhibit the growth of lung adenocarcinoma A549-Homo BIRC5 xenograft tumors in nude mice.