双亚苄基哌啶与蛋白酶体抑制剂对舌癌细胞毒性作用及机制  

Toxic effect and mechanism of Bis-Benzylidine Piperidon and proteasome inhibitor on tongue cancer cells

作　　者：陈静坤 叶展超[1] 郑晓辉 张锦雀 CHEN Jing-kun;YE Zhan-chao;ZHENG Xiao-hui;ZHANG Jin-que(Dept of Stomatology,Zhongshan Hospital Affiliated to Xiamen University,Xiamen Fujian 361000,China;Fujian Provincial Key Lab of Functional and Clinical Translational Medicine,Xiamen Medical College,Xiamen Fujian 361023,China;Fujian Medical University Affiliated Stomatological Hospital,Fuzhou 351004,China)

机构地区：[1]厦门大学附属中山医院口腔科,福建厦门361000 [2]厦门医学院机能与临床转化福建省高校重点实验室,福建厦门361023 [3]福建医科大学附属口腔医院,福建福州351004

出　　处：《中国药理学通报》2020年第1期42-46,共5页Chinese Pharmacological Bulletin

基　　金：厦门医学院校级科研计划项目(No K2016-03);福建省中青年教师教育科研项目(No JAT160584)

摘　　要：目的探讨双亚苄基哌啶RA190与蛋白酶体抑制剂MG132对舌癌细胞CAL27、TCA8113的毒性作用及机制。方法将不同浓度的RA190或MG132作用于舌癌细胞24 h,CCK-8法检测各组细胞存活情况;流式分析不同组舌癌细胞周期与凋亡情况;Western blot检测各组细胞内ADRM1、Cyclin B1、Bak、Bax蛋白表达。结果RA190对CAL27、TCA8113的半抑制浓度IC 50分别约为0.18和1.6μmol·L-1;MG132的IC 50分别约为0.1和0.3μmol·L-1。RA190诱导CAL27细胞G 1/G 0或G 2/M期停滞;MG132诱导CAL27细胞G 2/M期停滞。1μmol·L-1 RA190提高TCA8113细胞凋亡率(P<0.05);MG132提高CAL27与TCA8113细胞凋亡率(P<0.05),并呈剂量依赖性。RA190和MG132均下调CAL27、TCA8113细胞内ADRM1、Bak、Bax蛋白表达,上调Cyclin B1。结论RA190在舌癌中作用具有较大的选择性和局限性,采用靶向ADRM1治疗策略不适用于舌癌。MG132通过ADRM1以外的其他通路对舌癌细胞产生毒性作用;MG132可能应用于舌癌治疗,但存在的副作用也可能较广。Aim To investigate the toxic effects dibenzylidene piperidine RA190 and proteasome inhibitor MG132 on tongue cancer cell line CAL27 and TCA8113 and its mechanisms.Methods Different concentrations of RA190 or MG132 were exposed to tongue cancer cells for 24 hours.CCK-8 assay was used to detect the survival of CAL27 and TCA8113 cells,and flow cytometry was used to analyze the cell cycle and apoptosis of different groups of tongue cancer cells.Western blot was used to detect the expression of ADRM1,Cyclin B1,Bak and Bax protein in each group.Results The semi-inhibitory(IC 50)concentration of RA190 on CAL27 and TCA8113 was about 0.18 and 1.6μmol·L-1 respectively,while the IC 50 of MG132 was about 0.1 and 0.3μmol·L-1 respectively.RA190 induced CAL27 cell G 1/G 0 phase or G 2/M phase arrest,while MG132 induced CAL27 cell G 2/M phase arrest.1μmol·L-1 RA190 increased the apoptotic rate of TCA8113 cells(P<0.05);MG132 significantly increased the apoptotic rate of CAL27 and TCA8113 cells(P<0.05),and the apoptotic rate of CAL27 and TCA8113 cells significantly increased in a dose-dependent manner.RA190 and MG132 both down-regulated ADRM1,Bak and Bax protein,and up-regulated Cyclin B1 in CAL27 and TCA8113 cells.Conclusions RA190 has great selectivity and limitation in tongue cancer.Targeted ADRM1 therapy is not suitable for tongue cancer.MG132 has toxic effect on tongue cancer cells through pathways other than ADRM1.MG132 may be used in treatment of tongue cancer,but the side effects may be wide.

关 键 词：RA190 MG132 ADRM1 舌癌 细胞毒性 周期 凋亡 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学] R329[医药卫生—基础医学]