朱砂莲甲素对口腔鳞癌大鼠模型P63、TRPM8的影响
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摘要
目的探讨朱砂莲甲素对口腔鳞癌大鼠模型P63、TRPM8的影响。方法选取20只Wistar大鼠制作口腔鳞癌模型,成功16只,分为模型组和朱砂莲甲素组,每组8只;另外选择10只Wistar大鼠作为正常组。朱砂莲甲素组给予朱砂莲甲素进行治疗,其余2组大鼠采用无菌蒸馏水进行腹腔注射。3组大鼠进行平均体质量、肿瘤体积检查,病理形态学观察,采用Western blot检测P63、TRPM8、HGF、c-Met表达。结果模型组大鼠平均体质量低于正常组,肿瘤体积大于正常组,差异具有统计学意义(P <0. 05);朱砂莲甲素组大鼠平均体质量高于模型组,肿瘤体积小于模型组,差异具有统计学意义(P <0. 05)。模型组大鼠P63、TRPM8、HGF、c-Met水平高于正常组,差异具有统计学意义(P <0. 05);朱砂莲甲素组大鼠P63、TRPM8、HGF、c-Met低于模型组,差异具有统计学意义(P <0. 05)。结论朱砂莲甲素可有效减小口腔鳞癌大鼠肿瘤体积,通过调节HGF/c-Met信号通路改善P63、TRPM8水平,对临床治疗口腔鳞癌具有重要意义。
Objective To study the effect of emodin on P63 and TRPM8 of oral squamous cell carcinoma in rat model. Methods Twenty Wistar rats were selected to make oral squamous cell carcinoma models,16 of them were successfully divided into model group and emodin group,8 rats in each group. Another 10 Wistar rats were selected as the normal group. Emodin group was treated with emodin,the other two groups were injected with aseptic distilled water. The average body weight,tumor volume and pathomorphology of rats in 3 groups were examined,and the expressions of P63,TRPM8,HGF and c-Met were detected by Western blot. Results The average body weight of the model group was lower than that of normal group,and the tumor volume of the model group was larger than that of normal group,the differences were statistically significant( P < 0. 05). The average body weight of the emodin group was higher than that of model group,and the tumor volume of the emodin group was smaller than that of model group,the differences were statistically significant( P < 0. 05). The levels of P63,TRPM8,HGF and c-Met in model group were higher than those in normal group,the differences were statistically significant( P < 0. 05). The levels of P63,TRPM8,HGF,c-Met in emodin group were lower than those in model group,the differences were statistically significant( P < 0. 05). Conclusion Emodin can effectively reduce the tumor volume of oral squamous cell carcinoma in rats,which regulates HGF/cMet signaling pathway to improve P63 and TRPM8 levels. It is important for clinical treatment of oral squamous cell carcinoma.
Objective To study the effect of emodin on P63 and TRPM8 of oral squamous cell carcinoma in rat model. Methods Twenty Wistar rats were selected to make oral squamous cell carcinoma models,16 of them were successfully divided into model group and emodin group,8 rats in each group. Another 10 Wistar rats were selected as the normal group. Emodin group was treated with emodin,the other two groups were injected with aseptic distilled water. The average body weight,tumor volume and pathomorphology of rats in 3 groups were examined,and the expressions of P63,TRPM8,HGF and c-Met were detected by Western blot. Results The average body weight of the model group was lower than that of normal group,and the tumor volume of the model group was larger than that of normal group,the differences were statistically significant( P < 0. 05). The average body weight of the emodin group was higher than that of model group,and the tumor volume of the emodin group was smaller than that of model group,the differences were statistically significant( P < 0. 05). The levels of P63,TRPM8,HGF and c-Met in model group were higher than those in normal group,the differences were statistically significant( P < 0. 05). The levels of P63,TRPM8,HGF,c-Met in emodin group were lower than those in model group,the differences were statistically significant( P < 0. 05). Conclusion Emodin can effectively reduce the tumor volume of oral squamous cell carcinoma in rats,which regulates HGF/cMet signaling pathway to improve P63 and TRPM8 levels. It is important for clinical treatment of oral squamous cell carcinoma.
引文
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[9]高路.绿茶提取物对口腔鳞癌模型大鼠抗肿瘤组织中EphA2、EphrinA1和E-cadherin表达的影响[J].西部中医药,2018,31(4):25-28.
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[11]梁洪华.萝卜硫素对缺氧肺动脉平滑肌细胞增殖和迁移影响的研究[D].南宁:广西医科大学,2017.
[12]陈建霖,杨喆,周力,等.p16、p53及p63在口腔鳞癌及癌前病变组织中的表达[J].宁夏医学杂志,2016,38(10):875-878.doi:10.13621/j.1001-5949.2016.10.0875.
[13]韩江.E-cadherin和P63蛋白在宫颈癌组织中的表达及与临床病理特征的关系研究[J].中国妇幼保健,2016,31(19):4048-4050.doi:10.7620/zgfybj.j.issn.1001-4411.2016.19.65.
[14]陈晨,刘兆国,汪思亮,等.薄荷醇及其受体TRPM8与肿瘤关系研究进展[J].中国药理学通报,2015,31(3):312-314.doi:10.3969/j.issn.1001-1978.2015.03.004.
[15]Bidaux G,Borowiec AS,Dubois C,et al.Targeting of short TRPM8 isoforms induces 4TM-TRPM8-dependent apoptosis in prostate cancer cells[J].Oncotarget,2016,7(20):29063-29080.doi:10.18632/oncotarget.8666.
[16]刘涛,陶皇恒,方志海,等.TRPM8抑制剂BCTC对前列腺癌DU145细胞的抑癌作用[J].武汉大学学报(医学版),2015,36(2):225-230.doi:10.14188/j.1671-8852.2015.02.01.
[17]Liu J,Chen Y,Shuai S,et al.Trpm8 promotes aggressiveness of breast cancer cells by regulating emt via activating akt/gsk-3βpathway[J].Tumour Biol,2014,35(9):8969-8977.doi:10.1007/s13277-014-2077-8.
[18]罗朝阳,陈仲伟.HGF/c-Met信号通路及其与口腔鳞癌关系研究进展[J].广东牙病防治,2014,22(9):497-501.
[19]杜洪亮,何等旗,于涛,等.肝细胞生长因子对口腔鳞癌裸鼠移植瘤的作用及其机制研究[J].实用口腔医学杂志,2018,34(5):586-590.doi:10.3969/j.issn.1001-3733.2018.05.002.
[20]吕洁,张德保,陈建,等.c-Met蛋白与HGF蛋白在舌鳞癌细胞中的表达及临床意义[J].西安交通大学学报(医学版),2015,36(2):245-248.doi:10.7652/jdyxb201502020.
[21]Kwon Y,Godwin AK.Regulation of HGF and c-Met interaction in normal ovary and ovarian cancer[J].Reprod Sci,2017,24(4):494-501.doi:10.1177/1933719116648212.
[22]张敏,雷志敏,闫国胜,等.HGF/c-Met、VEGF和uPA在口腔鳞癌组织中的表达及意义[J].临床口腔医学杂志,2010,26(1):8-11.doi:10.3969/j.issn.1003-1634.2010.01.003.
[23]Chen X,Zhang S,Chen X,et al.Emodin promotes the osteogenesis of MC3T3-E1 cells via BMP-9/Smad pathway and exerts a preventive effect in ovariectomized rats[J].Acta Biochim Biophys Sin(Shanghai),2017,49(10):867-878.doi:10.1093/abbs/gmx087.
[24]党中峰,党雅梅,陈城,等.大黄素诱导对内质网应激相关蛋白表达及肝癌HepG2细胞凋亡的影响[J].兰州大学学报(医学版),2015,41(2):50-54.doi:10.13885/j.issn.1000-2812.2015.02.010.
[25]张凯亮,焦康礼,朱玉娟,等.大黄素抑制人口腔鳞癌细胞Tca8113增殖及细胞周期进程的实验研究[J].南方医科大学学报,2015,35(5):665-670.doi:10.3969/j.issn.1673-4254.2015.05.08.
[2]Kao SS,Peters MD,Krishnan SG,et al.Swallowing outcomes following primary surgical resection and primary free flap reconstruction for oral and oropharyngeal squamous cell carcinomas:a systematic review[J].Laryngoscope,2016,126(7):1572-1580.doi:10.1002/lary.25894.
[3]Manimaran A,Buddhan R,Manoharan S.Emodin downregulates cell proliferation markers during dmba induced oral carcinogenesis in golden syrian hamsters[J].Afr J Tradit Complement Altern Med,2017,14(2):83-91.doi:10.21010/ajtcam.v14i2.10.
[4]Monteiro LS,Delgado ML,Ricardo S,et al.Prognostic significance of cd44v6,p63,podoplanin and mmp-9 in oral squamous cell carcinomas[J].Oral Dis,2016,22(4):303-312.doi:10.1111/odi.12442.
[5]李宏维,周斌,张海鸿.TRPM8通过c AMP-PKA/UCP4信号调控氧糖剥夺/复糖复氧诱导的神经元凋亡[J].南方医科大学学报,2016,36(9):1265-1270.doi:10.3969/j.issn.1673-4254.2016.09.18.
[6]董正,陈超,董绪德,等.TRPM8离子通道在胰腺癌中高表达的临床意义[J].中华肝胆外科杂志,2017,23(10):680-684.doi:10.3760/cma.j.issn.1007-8118.2017.10.008.
[7]De Pazo,Kao HK,HY,et al.Prognostic stratification of patients with advanced oral cavity squamous cell carcinoma[J].Curr Oncol Rep,2017,19(10):65.doi:10.1007/s11912-017-0624-3.
[8]Gelwan E,Malm IJ,Khararjian A,et al.Nonuniform distribution of highrisk human papillomavirus in squamous cell carcinomas of the oropharynx:rethinking the anatomic boundaries of oral and oropharyngeal carcinoma from an oncologic HPV perspective[J].Am J Surg Pathol,2017,41(12):1722-1728.doi:10.1097/PAS.0000000000000929.
[9]高路.绿茶提取物对口腔鳞癌模型大鼠抗肿瘤组织中EphA2、EphrinA1和E-cadherin表达的影响[J].西部中医药,2018,31(4):25-28.
[10]廖鹏程,张绪,谭红,等.屏障环境下建立4NQO饮水诱导SD大鼠口腔鳞癌模型[J].广东牙病防治,2015,23(2):66-70.
[11]梁洪华.萝卜硫素对缺氧肺动脉平滑肌细胞增殖和迁移影响的研究[D].南宁:广西医科大学,2017.
[12]陈建霖,杨喆,周力,等.p16、p53及p63在口腔鳞癌及癌前病变组织中的表达[J].宁夏医学杂志,2016,38(10):875-878.doi:10.13621/j.1001-5949.2016.10.0875.
[13]韩江.E-cadherin和P63蛋白在宫颈癌组织中的表达及与临床病理特征的关系研究[J].中国妇幼保健,2016,31(19):4048-4050.doi:10.7620/zgfybj.j.issn.1001-4411.2016.19.65.
[14]陈晨,刘兆国,汪思亮,等.薄荷醇及其受体TRPM8与肿瘤关系研究进展[J].中国药理学通报,2015,31(3):312-314.doi:10.3969/j.issn.1001-1978.2015.03.004.
[15]Bidaux G,Borowiec AS,Dubois C,et al.Targeting of short TRPM8 isoforms induces 4TM-TRPM8-dependent apoptosis in prostate cancer cells[J].Oncotarget,2016,7(20):29063-29080.doi:10.18632/oncotarget.8666.
[16]刘涛,陶皇恒,方志海,等.TRPM8抑制剂BCTC对前列腺癌DU145细胞的抑癌作用[J].武汉大学学报(医学版),2015,36(2):225-230.doi:10.14188/j.1671-8852.2015.02.01.
[17]Liu J,Chen Y,Shuai S,et al.Trpm8 promotes aggressiveness of breast cancer cells by regulating emt via activating akt/gsk-3βpathway[J].Tumour Biol,2014,35(9):8969-8977.doi:10.1007/s13277-014-2077-8.
[18]罗朝阳,陈仲伟.HGF/c-Met信号通路及其与口腔鳞癌关系研究进展[J].广东牙病防治,2014,22(9):497-501.
[19]杜洪亮,何等旗,于涛,等.肝细胞生长因子对口腔鳞癌裸鼠移植瘤的作用及其机制研究[J].实用口腔医学杂志,2018,34(5):586-590.doi:10.3969/j.issn.1001-3733.2018.05.002.
[20]吕洁,张德保,陈建,等.c-Met蛋白与HGF蛋白在舌鳞癌细胞中的表达及临床意义[J].西安交通大学学报(医学版),2015,36(2):245-248.doi:10.7652/jdyxb201502020.
[21]Kwon Y,Godwin AK.Regulation of HGF and c-Met interaction in normal ovary and ovarian cancer[J].Reprod Sci,2017,24(4):494-501.doi:10.1177/1933719116648212.
[22]张敏,雷志敏,闫国胜,等.HGF/c-Met、VEGF和uPA在口腔鳞癌组织中的表达及意义[J].临床口腔医学杂志,2010,26(1):8-11.doi:10.3969/j.issn.1003-1634.2010.01.003.
[23]Chen X,Zhang S,Chen X,et al.Emodin promotes the osteogenesis of MC3T3-E1 cells via BMP-9/Smad pathway and exerts a preventive effect in ovariectomized rats[J].Acta Biochim Biophys Sin(Shanghai),2017,49(10):867-878.doi:10.1093/abbs/gmx087.
[24]党中峰,党雅梅,陈城,等.大黄素诱导对内质网应激相关蛋白表达及肝癌HepG2细胞凋亡的影响[J].兰州大学学报(医学版),2015,41(2):50-54.doi:10.13885/j.issn.1000-2812.2015.02.010.
[25]张凯亮,焦康礼,朱玉娟,等.大黄素抑制人口腔鳞癌细胞Tca8113增殖及细胞周期进程的实验研究[J].南方医科大学学报,2015,35(5):665-670.doi:10.3969/j.issn.1673-4254.2015.05.08.