奥曲肽对胰腺癌模型大鼠细胞凋亡的影响及作用机制研究
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摘要
目的探究奥曲肽对胰腺癌模型大鼠细胞凋亡的影响及相关作用机制。方法选取50只SD健康雄性大鼠,随机选取10只作为正常组,其余40只大鼠进行胰腺癌模型建立,并将胰腺癌模型大鼠随机分为模型组以及低、中、高剂量奥曲肽组,正常组、模型组大鼠使用生理盐水进行干预,低、中、高剂量奥曲肽组大鼠使用不同剂量奥曲肽进行干预。对比各组大鼠肿瘤体积、质量以及肿瘤细胞凋亡、周期分布情况,Western blot法检测Bcl-2、PI3K、Akt、PTEN、p-Akt、m TOR表达。结果高剂量奥曲肽组大鼠肿瘤体积、质量均低于低、中剂量奥曲肽组(P均<0. 05)。高剂量奥曲肽组大鼠肿瘤细胞凋亡率高于低、中剂量奥曲肽组(P均<0. 05)。高剂量奥曲肽组处于G1期的细胞比例高于低、中剂量奥曲肽组(P均<0. 05)。高剂量奥曲肽组Bcl-2、PI3K、Akt、p-Akt、m TOR相对表达量均低于低、中剂量奥曲肽组(P均<0. 05); PTEN相对表达量高于低、中剂量奥曲肽组(P均<0. 05)。结论使用较高剂量奥曲肽对胰腺癌模型大鼠进行干预,能够使大鼠肿瘤体积、质量下降,调控细胞凋亡相关蛋白Bcl-2、PI3K、Akt以及周期相关蛋白PTEN、p-Akt、m TOR的表达,从而促进细胞凋亡,改善细胞周期分布,为胰腺癌的治疗提供理论帮助。
Objective To explore the effect of octreotide on apoptosis of pancreatic cancer model rats and its related mechanism.Methods Fifty healthy male SD rats were randomly selected as normal group, and the remaining 40 rats were used to establish pancreatic cancer model. The pancreatic cancer model rats were randomly divided into model group and low, medium and high dose octreotide group. Normal and model rats were intervened with normal saline, while low, medium and high dose octreotide groups were intervened with different doses of octreotide. Western blot was used to detect the expression of Bcl-2, PI3 K, Akt, PTEN, p-Akt and m TOR. Results The tumor volume and weight of the high-dose octreotide group were lower than those of the low-dose and mediumdose octreotide group( P < 0. 05). The apoptosis rate of tumor cells in high-dose octreotide group was higher than that in low-dose and medium-dose octreotide group( P < 0. 05). The proportion of cells in G1 phase in the high-dose octreotide group was higher than that in the low-dose and medium-dose octreotide group( P < 0. 05). The relative expression levels of bcl-2, PI3 K and Akt in the high-dose octreotide group were lower than those in the low-dose and medium-dose octreotide group( P < 0. 05). The relative expression levels of PTEN in the high-dose octreotide group were higher than those in the low-dose and medium-dose octreotide group, and the relative expression levels of p-akt and m TOR were lower than those in the low-dose and medium-dose octreotide group( P < 0. 05). Conclusion The intervention of high dose octreotide on pancreatic cancer model rats can reduce the volume and weight of the tumors, regulate the expression of Bcl-2, PI3 K, Akt, PTEN, p-Akt and m TOR, so as to promote cell apoptosis, improve cell cycle distribution and provide theoretical help for the treatment of pancreatic cancer.
Objective To explore the effect of octreotide on apoptosis of pancreatic cancer model rats and its related mechanism.Methods Fifty healthy male SD rats were randomly selected as normal group, and the remaining 40 rats were used to establish pancreatic cancer model. The pancreatic cancer model rats were randomly divided into model group and low, medium and high dose octreotide group. Normal and model rats were intervened with normal saline, while low, medium and high dose octreotide groups were intervened with different doses of octreotide. Western blot was used to detect the expression of Bcl-2, PI3 K, Akt, PTEN, p-Akt and m TOR. Results The tumor volume and weight of the high-dose octreotide group were lower than those of the low-dose and mediumdose octreotide group( P < 0. 05). The apoptosis rate of tumor cells in high-dose octreotide group was higher than that in low-dose and medium-dose octreotide group( P < 0. 05). The proportion of cells in G1 phase in the high-dose octreotide group was higher than that in the low-dose and medium-dose octreotide group( P < 0. 05). The relative expression levels of bcl-2, PI3 K and Akt in the high-dose octreotide group were lower than those in the low-dose and medium-dose octreotide group( P < 0. 05). The relative expression levels of PTEN in the high-dose octreotide group were higher than those in the low-dose and medium-dose octreotide group, and the relative expression levels of p-akt and m TOR were lower than those in the low-dose and medium-dose octreotide group( P < 0. 05). Conclusion The intervention of high dose octreotide on pancreatic cancer model rats can reduce the volume and weight of the tumors, regulate the expression of Bcl-2, PI3 K, Akt, PTEN, p-Akt and m TOR, so as to promote cell apoptosis, improve cell cycle distribution and provide theoretical help for the treatment of pancreatic cancer.
引文
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[5]王云检,张珉,蒙博,等.大黄牡丹汤对胰腺癌大鼠的治疗作用和肝肾保护作用[J].吉林大学学报(医学版),2017,43(6):1069-1073.
[6]郭飞波,韩利蓉,余卉,等. miR-43、miR-45在胰腺癌患者血清中的表达情况及与患者临床参数的相关性分析[J].中国免疫学杂志,2018,34(10):1547-1551.
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[9]聂钊,李岚,杨兰群,等.胰腺癌组织中PSAT1表达及其介导的细胞增殖侵袭作用机制研究[J].中国肿瘤临床,2018,45(23):1187-1193.
[10]朱兴兴,陈炯,徐弘,等. UL16结合蛋白在胰腺癌中的表达及其临床意义[J].安徽医科大学学报,2017,52(2):232-235.
[11]邓超,李景辉,吴平安,等.奥曲肽联合乌司他丁治疗急性重症胰腺炎的临床研究[J].中国临床药理学杂志,2016,32(18):1653-1656.
[12]叶倩倩,钟继红.奥曲肽辅助治疗对急性胰腺炎患者血清CRP、淀粉酶水平影响研究[J].中国生化药物杂志,2016,36(1):106-108.
[13]吴晓光,仇志富,孟杰,等.补阳还五汤对脑出血模型大鼠脑组织PI3K、Akt、Bcl-2、BAX蛋白表达的影响[J].中国组织工程研究,2016,20(40):5933-5938.
[14]郑志强,郑继行,蔡振寨,等. Lxn对CD133+PANC-1胰腺癌细胞增殖及bcl-2、bax表达的影响[J].中华普通外科杂志,2016,31(1):46-49.
[15]林贤东,胡丹,陈刚,等. PI3K-AKT-mTOR信号通路基因多态性与胃癌遗传易感相关性[J].临床与实验病理学杂志,2016,32(4):361-365,369.
[16]祁迪,谭群友,王如文,等.吴茱萸碱抑制PI3K/AKT通路诱导小细胞肺癌H1688和H446细胞凋亡[J].第三军医大学学报,2016,38(4):330-337.
[17]邹曰坤,石志远,易竟,等.过表达PTEN对LPS诱导的成纤维细胞周期及胶原分泌的影响[J].国际检验医学杂志,2017,38(9):1190-1191,1195.
[18]潘学洪,王晓东.抑制Akt信号通路对病理性瘢痕成纤维细胞生长、细胞周期及凋亡的影响[J].郑州大学学报(医学版),2018,53(2):229-233.
[19]冯楠楠,王冰洁,朱启航,等.玉米赤霉烯酮通过PI3K/Akt/m TOR通路诱导大鼠睾丸支持细胞自噬及对细胞周期分布的影响[J].南京农业大学学报,2018,41(4):708-714.
[20]徐萍,蒋小猛,葛璐,等.二甲双胍对人胰腺癌细胞增殖、细胞周期和凋亡的影响及机制[J].中国现代医学杂志,2018,28(1):1-5.
[2] Ilic M,Ilic I. Epidemiology of pancreatic cancer[J]. World J Gastroenterol,2016,22(44):9694-9705.
[3]王维斌,董良博,赵邦博,等.法尼醇X受体表达与胰腺癌患者预后及病理分期相关[J].基础医学与临床,2018,38(3):394-399.
[4]崔江河,韩光宇,何光梅,等.人参皂苷CK联合5-氟尿嘧啶对人胰腺癌PANC-1细胞的增殖、凋亡及上皮间质转化的影响[J].中国药房,2017,28(31):4388-4392.
[5]王云检,张珉,蒙博,等.大黄牡丹汤对胰腺癌大鼠的治疗作用和肝肾保护作用[J].吉林大学学报(医学版),2017,43(6):1069-1073.
[6]郭飞波,韩利蓉,余卉,等. miR-43、miR-45在胰腺癌患者血清中的表达情况及与患者临床参数的相关性分析[J].中国免疫学杂志,2018,34(10):1547-1551.
[7] Chu LC,Goggins MG,Fishman EK. Diagnosis and Detection of Pancreatic Cancer[J]. Cancer J,2017,23(6):333-342.
[8]赵甦,崔卫东,宋伟华,等. survivin和caspase 3蛋白在胰腺癌组织中的表达及与胰腺癌患者临床特征的关系[J].癌症进展,2018,16(10):1275-1277,1287.
[9]聂钊,李岚,杨兰群,等.胰腺癌组织中PSAT1表达及其介导的细胞增殖侵袭作用机制研究[J].中国肿瘤临床,2018,45(23):1187-1193.
[10]朱兴兴,陈炯,徐弘,等. UL16结合蛋白在胰腺癌中的表达及其临床意义[J].安徽医科大学学报,2017,52(2):232-235.
[11]邓超,李景辉,吴平安,等.奥曲肽联合乌司他丁治疗急性重症胰腺炎的临床研究[J].中国临床药理学杂志,2016,32(18):1653-1656.
[12]叶倩倩,钟继红.奥曲肽辅助治疗对急性胰腺炎患者血清CRP、淀粉酶水平影响研究[J].中国生化药物杂志,2016,36(1):106-108.
[13]吴晓光,仇志富,孟杰,等.补阳还五汤对脑出血模型大鼠脑组织PI3K、Akt、Bcl-2、BAX蛋白表达的影响[J].中国组织工程研究,2016,20(40):5933-5938.
[14]郑志强,郑继行,蔡振寨,等. Lxn对CD133+PANC-1胰腺癌细胞增殖及bcl-2、bax表达的影响[J].中华普通外科杂志,2016,31(1):46-49.
[15]林贤东,胡丹,陈刚,等. PI3K-AKT-mTOR信号通路基因多态性与胃癌遗传易感相关性[J].临床与实验病理学杂志,2016,32(4):361-365,369.
[16]祁迪,谭群友,王如文,等.吴茱萸碱抑制PI3K/AKT通路诱导小细胞肺癌H1688和H446细胞凋亡[J].第三军医大学学报,2016,38(4):330-337.
[17]邹曰坤,石志远,易竟,等.过表达PTEN对LPS诱导的成纤维细胞周期及胶原分泌的影响[J].国际检验医学杂志,2017,38(9):1190-1191,1195.
[18]潘学洪,王晓东.抑制Akt信号通路对病理性瘢痕成纤维细胞生长、细胞周期及凋亡的影响[J].郑州大学学报(医学版),2018,53(2):229-233.
[19]冯楠楠,王冰洁,朱启航,等.玉米赤霉烯酮通过PI3K/Akt/m TOR通路诱导大鼠睾丸支持细胞自噬及对细胞周期分布的影响[J].南京农业大学学报,2018,41(4):708-714.
[20]徐萍,蒋小猛,葛璐,等.二甲双胍对人胰腺癌细胞增殖、细胞周期和凋亡的影响及机制[J].中国现代医学杂志,2018,28(1):1-5.