基于小鼠黑色素瘤肺转移模型探讨丙泊酚上调DR5表达发挥抑瘤作用的研究  

Study on the inhibitory effect of propofol on upregulation of DR5 expression based on mouse melanoma lung metastasis model

作　　者：周超瑞 马伟斌 叶孝乾 陈娜 李明娟[4] ZHOU Chao-rui;MA Wei-bin;YE Xiao-qian;CHEN Na;LI Ming-juan(Department of Anesthesiology,China Coast Guard Hospital of the People’s Armed Police Force,Jiaxing,Zhejiang 314000,China;不详)

机构地区：[1]海警医院麻醉科,浙江嘉兴314000 [2]浙江中医药大学研究生院,浙江杭州310053 [3]海警医院病理科 [4]嘉兴学院医学院,浙江嘉兴314001

出　　处：《中华全科医学》2022年第7期1126-1130,共5页Chinese Journal of General Practice

基　　金：浙江省基础公益研究项目(LGD21H300001)。

摘　　要：目的恶性黑色素瘤是一种恶性化程度高、易转移的由黑色素细胞恶性增殖引起的皮肤癌。本研究旨在探讨丙泊酚对小鼠B16F10黑色素瘤肺转移的抑制作用,以期为丙泊酚是否更适用于黑色素瘤相关手术麻醉提供一定的理论基础。方法体外细胞实验采用CCK-8方法考察不同浓度的丙泊酚对B16F10细胞增殖的抑制作用;流式细胞术检测不同实验组B16F10细胞凋亡率;Western blotting法检测各实验组DR5蛋白表达的变化。体内实验采用尾静脉注射B16F10细胞方法建立模型组,将C57BL/6J雄性小鼠24只,采用随机数字表法分为4组,即正常对照组,黑色素瘤肺转移模型组,丙泊酚50 mg/kg、10 mg/kg剂量组,每组6只,观察腹腔注射丙泊酚对小鼠肺组织肿瘤转移结节的影响。结果体外实验结果显示,对照组与10μmol/L、50μmol/L、100μmol/L 3个浓度实验组于72 h时的细胞相对增殖能力(490 nm OD值)分别为0.91±0.03、0.81±0.02、0.71±0.02和0.61±0.02;100μmol/L丙泊酚处理B16F10细胞在24 h、48 h和72 h三个时间点的细胞凋亡率分别为(8.09±1.01)%、(26.04±1.10)%、(32.94±1.30)%,100μmol/L丙泊酚处理B16F10细胞72 h,DR5蛋白表达显著上调。体内实验证实,50 mg/kg剂量的丙泊酚腹腔注射可以显著抑制肺转移黑色素瘤的结节数,且免疫组化结果显示,丙泊酚组肺组织中DR5的表达显著增加。结论丙泊酚能够抑制小鼠肺转移黑色素瘤,其机制可能与上调DR5蛋白表达相关。Objective Melanoma is a skin cancer caused by a malignancy of melanocytes.The incidence of melanoma is rapidly increasing worldwide,thus resulting in public health problems.Surgical resection is still the main method of early treatment.As a commonly used intravenous general anaesthesia drug,propofol has been reported to have a certain inhibitory effect on cell proliferation.This study aims to explore the inhibitory effect of propofol on lung metastasis of B16 F10 melanoma in mice to provide a theoretical basis for propofol to be more suitable for surgical anaesthesia of malignant melanoma.Methods Cell viability was measured by CCK-8 assay.Flow cytometry was used to detect the apoptotic rate and Western blotting was used to detect the expression of DR5.In the in-vivo experiment,tumour cells were injected into the caudal vein to establish a lung metastatic model.Twenty-four male C57 BL/6 J mice were divided into 4 groups by random number table method,namely normal control group,melanoma lung metastasis model group,propofol 50 mg/kg,10 mg/kg groups,6 mice in each group.The effect of intraperitoneal injection of propofol on tumour metastatic nodules in the lung tissue of mice was observed.Results In the in-vitro experiment,the relative proliferation capacity(490 nm OD value)of cells in the control group and 10μmol/L,50μmol/L,100μmol/L groups at 72 h were 0.91±0.03,0.81±0.02,0.71±0.02 and 0.61±0.02,respectively.The apoptotic rates of B16 F10 cells treated with 100μmol/L propofol were(8.09±1.01)%,(26.04±1.10)%,(32.94±1.30)% at 24,48 and 72 h,respectively.In the in-vivo experiment,intraperitoneal injection of propofol at a dose of 50 mg/kg could significantly inhibit the number of nodules in lung metastatic melanoma and the immunohistochemical results showed that the expression of DR5 in lung tissue significantly increased in the propofol group.Conclusion Propofol could inhibit lung metastatic melanoma in mice and the mechanism may be related to the up-regulation of DR5 protein expression.

关 键 词：恶性黑色素瘤 丙泊酚 死亡受体5 增殖 凋亡 

分 类 号：R739.5[医药卫生—肿瘤] R73-3[医药卫生—临床医学]