Effects of beta-adrenergic receptor blockers and COX-2 inhibitors on liver metastasis of colorectal cancer

doi:10.12092/j.issn.1009-2501.2018.08.009

Abstract

Abstract:

AIM: To study the role and potential mechanism of β-adrenergic receptor blockers and COX-2 inhibitors in liver metastasis of colorectal cancer. METHODS: The effect of different concentrations of β-adrenoceptor blockers and COX-2 inhibitors on colon cancer cell proliferation, VEGF secretion and ROS expression were investigated by in vitro colorectal cancer cell experiments. Then, animal models of liver metastasis of colorectal cancer were performed. The tumor metastasis rate, tumor number, maximum tumor weight, maximum tumor diameter, and VEGF mRNA were measured. RESULTS:β-adrenergic receptor blockers and COX-2 inhibitors had significant proliferation-inhibitory effects on colon cancer cells in a dose-dependent manner. When the concentration of β-adrenergic receptor blocker was 200 μmol/L, the tumor cell proliferation inhibition rate was (39.00±2.00)% and the VEGF secretion was (55.44±7.65) pg/mL. And the tumor cell proliferation inhibition rate was (33.67±1.15)%, and the VEGF secretion was (37.75±4.08) pg/mL when the concentration of COX-2 inhibitor was 2 μmol/L. The difference was statistically significant in each group (P<0.05). Compared with the use of β-adrenergic receptor blockers, the use of COX-2 inhibitors significantly inhibited the growth of liver metastases, the difference was statistically significant (P<0.05).Combining β-adrenergic receptor blockers with COX-2 inhibitors could effectively reduce tumor maximal weight, size, and VEGF mRNA expression levels ［（0.20±0.13）g, （1.98±0.33）mm and 0.22±0.06］ as compared with the control group ［（0.88±0.13）g, （5.45±0.88）mm and 1.03±0.14］ and the β-adrenergic receptor blocker group ［（0.50±0.16）g,（3.45±0.45）mm and 0.75±0.08］ and the COX-2 inhibitor group ［（0.34±0.09）g, 2.73±0.24）mm and 0.50±0.08］, the difference was statistically significant (P<0.05). CONCLUSION: In the process of hepatic metastasis of colorectal cancer, β-adrenergic Receptor blocker and COX-2 inhibitors promote tumor cell apoptosis by regulating tumor expression of ROS, regulating VEGF secretion in tumor cells through synergistic action, and inhibiting neovascularization and migration of tumor cells.

Key words: beta-adrenergic receptor, COX-2, VEGF

CLC Number:

R735

LI Minjiang, CHEN Dong, CHEN Wenbin. Effects of beta-adrenergic receptor blockers and COX-2 inhibitors on liver metastasis of colorectal cancer[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(8): 893-899.

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