Muscarinic cholinergic receptor antagonist inhibits the growth and angiogenesis of small cell lung cancer in vivo / 肿瘤

ABSTRACT

Objective: To investigate the effects of muscarinic cholinergic receptor 3 (M3R) antagonist 4-diphenylacetoxy-N -methylpiperidine methiodide (4-DAMP) on the growth of small cell lung cancer and angiogenesis in nude mice. Methods: The mRNA and protein expressions of M3R in human small cell lung cancer SBC3 cells were detected by RT-PCR and Western blotting, respectively. The subcutaneous transplantation tumor model of SBC3 cells in nude mice was established. The model mice were randomly divided intofour groups, then intraperitoneally injected with 0.9% sodium chloride solution (as the control group) and different doses of 4-DAMP (0.5, 1 and 2 mg/kg), respectively (once a day, for 15 days). The size of xenograft tumor was measured every 2 days. After the nude mice were sacrificed, the tumor mass was measured, and the tumor inhibitory rate was calculated. The expressions of M3R and vascular endothelial growth factor (VEGF) in the tumor tissues were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. The microvessel density (MVD) and VEGF expression were detected by immunohistochemistry. Results: Human small cell lung cancer SBC3 cells expressed M3R mRNA and protein. After the subcutaneous transplantation tumor model of SBC3 cells in nude mice was successfully established and treated with different doses (0.5-2 mg/kg) of 4-DAMP, the sizes of xenograft tumors were significantly decreased as compared with the control group (all P < 0.05), and the weights of tumor tissues were significantly reduced (all P < 0.01). The tumor growth inhibitory rates in 0.5, 1 and 2 mg/kg 4-DAMP-treated groups were 15.82%, 33.54% and 55.06%, respectively. Furthermore, the relative expression levels of M3R and VEGF as well as MVD in the tumor tissues of 0.5, 1 and 2 mg/kg 4-DAMP-treated groups were significantly down-regulated as compared with the control group (all P < 0.05). Conclusion: M3R antagonist 4-DAMP can inhibit the growth and angiogenesis of human small cell lung cancer in nude mice.