健脾解毒方调节组蛋白去甲基化酶JMJD2C抑制结直肠癌转移  

Jianpi Jiedu Recipe inhibits colorectal cancer metastasis through regulating histone demethylase JMJD2C

作　　者：吴新楠 李瑞晓 李昊泽 浦匀舟 周晶 李琦[1,2,3] 季青[1,2] WU Xinnan;LI Ruixiao;LI Haoze;PU Yunzhou;ZHOU Jing;LI Qi;JI Qing(Department of Oncology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Cancer Institute,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Academy of Integrative Medicine,Shanghai University ol Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院肿瘤科,上海201203 [2]上海中医药大学附属曙光医院肿瘤研究所,上海201203 [3]上海中医药大学中西医结合研究院,上海201203

出　　处：《上海中医药大学学报》2021年第6期42-48,65,共8页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(82074225,81830120,81573749)。

摘　　要：目的:探讨健脾解毒方调节组蛋白去甲基化酶JMJD2C发挥抗结直肠癌转移的作用机制。方法:(1)取24只裸鼠,尾静脉注射结直肠癌HCT116细胞,复制结直肠癌肺转移模型。造模7 d后,将裸鼠平分为4组,分别灌胃给予不同剂量(0、250、500、1 000 mg/kg)的健脾解毒方水煎液。药物干预28 d后,分离肺转移灶组织,免疫组化检测JMJD2C蛋白表达。(2)分别以HCT116和LoVo细胞为研究对象,给予不同浓度(0、50、100、200μg/ml)健脾解毒方醇提液。药物干预48 h后,PCR检测JMJD2C mRNA表达,Western blot检测JMJD2C蛋白表达,免疫荧光检测JMJD2C的蛋白表达和细胞定位。结果:(1)健脾解毒方能够显著下调裸鼠结直肠癌肺转移灶中JMJD2C蛋白表达,且抑制作用呈剂量依赖性。(2)健脾解毒方能够显著下调两种结直肠癌细胞中JMJD2C的mRNA和蛋白表达,且100、200μg/ml作用更显著。(3)健脾解毒方能够抑制JMJD2C蛋白在结直肠癌细胞胞核内的累积,且100、200μg/ml作用更显著。结论:健脾解毒方能够抑制结直肠癌转移,作用机制可能与下调JMJD2C表达及其在细胞核的累积相关。Objective: To explore the mechanism of Jianpi Jiedu Recipe regulating histone demethylase JMJD2 C against colorectal cancer metastasis. Methods:(1)Twenty-four nude mice were taken and injected with colorectal cancer HCT116 cells via caudal vein, to replicate the lung metastasis model of colorectal cancer. Seven days after modeling, the nude mice were equally divided into four groups, and treated with Jianpi Jiedu Recipe decoction at different doses(0, 250, 500, 1 000 mg/kg) by intragastric administration. After drug treatment for 28 days, the lung metastasis tissue was isolated, and the expression of JMJD2 C protein was detected by immunohistochemistry.(2)HCT116 and LoVo cells were taken as the research objects, respectively. The cells were treated with alcohol extract of Jianpi Jiedu Recipe at different concentrations(0, 50, 100, 200 μg/ml). After drug treatment for 48 hours, the expression of JMJD2 C mRNA was detected by PCR, the expression of JMJD2 C protein was detected by Western blot, and the protein expression and cell localization of JMJD2 C were detected by immunofluorescence. Results:(1)Jianpi Jiedu Recipe could significantly down-regulate the expression of JMJD2 C protein in lung metastases of colorectal cancer in nude mice, and the inhibitory effect showed in a dose-dependentmanner.(2)Jianpi Jiedu Recipe could significantly down-regulate the mRNA and protein expressions of JMJD2 C in these two colorectal cancer cells, and Jianpi Jiedu Recipe at 100 and 200 μg/ml showed more significant effects.(3)Jianpi Jiedu Recipe could inhibit the accumulation of JMJD2 C protein in the nucleus of colorectal cancer cells, and Jianpi Jiedu Recipe at 100 and 200 μg/ml showed more significant effects.Conclusion: Jianpi Jiedu Recipe can inhibit the metastasis of colorectal cancer, and the mechanism may be related to the down-regulation of JMJD2 C expression and its accumulation in the nucleus.

关 键 词：健脾解毒方 组蛋白去甲基化酶JMJD2C 结直肠癌 转移 裸鼠 

分 类 号：R285[医药卫生—中药学]