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糖尿病及内分泌病学学术中心

慢性应激对结直肠癌模型中舒尼替尼抗血管生成的作用

The effect of chronic stress on anti-angiogenesis of sunitinib in colorectal cancer models

来源:Scopus 发布时间:2015-3-20
作者:Liu, J., Deng, G.-H., Zhang, J., Wang, Y., Xia, X.-Y., Luo, X.-M., Deng, Y.-T., He, S.-S., Mao, Y.-Y., Peng, X.-C., Wei, Y.-Q., Jiang, Y.
机构: 四川大学华西医院生物疗法国家重点实验室 癌症中心 医学肿瘤科
期刊: PSYCHONEUROENDOCRINO 2015年2月1期52卷

Epidemiological and experimental evidence has shown that psychological stress can propel cancer progression. However, its role in anti-angiogenic therapy is not well understood. We previously found that exogenous norepinephrine attenuated the effect of sunitinib, a multi-targeted anti-angiogenic agent, in a mouse melanoma model. Here, we further evaluated the effects of chronic stress on sunitinib therapy in colorectal cancer models. We found that chronic restraint stress markedly weakened the efficacy of sunitinib, primarily through promoting the expression of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) to stimulate tumor angiogenesis in vivo. This effect could be sufficiently mimicked by exogenous norepinephrine and blocked by the β-antagonist propranolol. In vitro, norepinephrine up-regulated expression of VEGF and IL-8 in sunitinib-treated cancer cells mainly through the β-adrenoceptor-cAMP-PKA signaling pathway. Norepinephrine also abrogated sunitinib-induced inhibition of cancer cell migration, but had no effect on direct anti-proliferative activity of sunitinib on cancer cells. These findings suggest that psychological stress might attenuate anti-angiogenic therapy primarily through activating beta-adrenergic signaling to promote tumor angiogenesis. It is also suggested that β-blockers might improve anti-angiogenic outcome under psychological stress.
 

通讯作者:Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
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