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脊髓EZH2参与大鼠骨癌疼痛发展的证据。

Evidence of the Involvement of Spinal EZH2 in the Development of Bone Cancer Pain in Rats.

作者信息

Chen Haoming, Yu Jianmang, Hang Lihua, Li Shuai, Lu Weikang, Xu Zhenkai

机构信息

Department of Anesthesiology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, 215300, People's Republic of China.

出版信息

J Pain Res. 2021 Nov 23;14:3593-3600. doi: 10.2147/JPR.S331114. eCollection 2021.

Abstract

INTRODUCTION

Bone cancer pain (BCP) seriously affects the quality of life of patients with advanced cancer, but effective treatment methods are lacking. This study mainly investigates the role of EZH2 in a well-established BCP model induced by Walker 256 breast cancer cells in rats.

METHODS

Female Sprague-Dawley rats of the same age weighing approximately 160 g were selected for the experiment. The BCP model was established by injecting inactivated Walker 256 breast cancer cells into the tibia. von Frey filaments were used to measure the paw withdrawal threshold, and bone destruction in the rat was observed using x-ray. The spinal EZH2 and H3K27Tm levels were measured using Western blotting and RT-qPCR analysis. Intrathecal injection of an EZH2 inhibitor was performed to examine the role of EZH2 in trigeminal BCP.

RESULTS

Experimental results showed that injecting Walker 256 breast cancer cells into the tibia induced bone cancer pain. Spinal EZH2 and H3K27Tm levels were significantly increased over time in BCP rats. An intrathecal injection of 3-deazaneplanocin A (DZNep), a selective EZH2 inhibitor, downregulated the expression of EZH2 and attenuate the BCP-induced mechanical allodynia state.

CONCLUSION

Intrathecal injection of DZNep relieve bone cancer pain in rats. EZH2 expressed in spinal cord tissue may be involved in the process of bone cancer pain in rats.

摘要

引言

骨癌疼痛(BCP)严重影响晚期癌症患者的生活质量,但缺乏有效的治疗方法。本研究主要探讨EZH2在Walker 256乳腺癌细胞诱导的大鼠骨癌疼痛模型中的作用。

方法

选取年龄相同、体重约160 g的雌性Sprague-Dawley大鼠进行实验。通过将灭活的Walker 256乳腺癌细胞注入胫骨建立骨癌疼痛模型。使用von Frey细丝测量爪部撤离阈值,并通过X射线观察大鼠的骨质破坏情况。采用蛋白质免疫印迹法和逆转录定量聚合酶链反应分析测量脊髓EZH2和H3K27Tm水平。进行鞘内注射EZH2抑制剂以研究EZH2在三叉神经骨癌疼痛中的作用。

结果

实验结果表明,将Walker 256乳腺癌细胞注入胫骨可诱导骨癌疼痛。在骨癌疼痛大鼠中,脊髓EZH2和H3K27Tm水平随时间显著升高。鞘内注射选择性EZH2抑制剂3-去氮杂氮胞苷(DZNep)可下调EZH2的表达,并减轻骨癌疼痛诱导的机械性异常疼痛状态。

结论

鞘内注射DZNep可减轻大鼠骨癌疼痛。脊髓组织中表达的EZH2可能参与大鼠骨癌疼痛的过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e0/8627314/282ca7a1888c/JPR-14-3593-g0001.jpg

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