阿来替尼对大鼠肺鳞癌中环氧化酶-2与半胱氨酸蛋白水解酶-3表达的影响
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摘要
目的研究阿来替尼对大鼠肺鳞癌中环氧化酶-2(COX-2)、半胱氨酸蛋白水解酶-3(Caspase-3)表达的影响。方法按照随机数表法将SD大鼠分成4组:正常组、模型组和低、高2个剂量实验组,每组13只。SD大鼠支气管灌注三甲基胆蒽6 mg和二乙基亚硝胺8 mg,建立大鼠肺鳞癌动物模型。造模成功后,实验组大鼠给予阿来替尼60,100 mg·kg~(-1)。取大鼠左肺叶下部的病灶组织,用免疫组化法测定肺鳞癌中COX-2、Caspase-3表达水平;计算大鼠的生存时间与生命延长率。结果模型组与低、高2个剂量实验组的生存时间分别为(25. 3±2. 9),(36. 0±2. 4),(47. 8±2. 6) d; 2个剂量实验组与模型组比较,差异均有统计学意义(均P <0. 05)。用药第15天,正常组、模型组和低、高2个剂量实验组的COX-2表达水平(IOD值)分别是0. 41±0. 14,1. 42±0. 22,0. 97±0. 21和0. 76±0. 15;这4组的Caspase-3表达水平(IOD值)分别是1. 71±0. 18,0. 56±0. 13,1. 01±0. 16和1. 29±0. 19。模型组与正常组比较,差异均有统计学意义(均P <0. 05);低、高2个剂量实验组与模型组比较,差异均有统计学意义(均P <0. 05),且高剂量实验组优于低剂量实验组。结论阿来替尼能使肺鳞癌大鼠的生存时间延长与生命质量提高,这可能与减少COX-2表达与上调肺鳞癌中Caspase-3表达有关。
Objective To study the effects of alittinib on the expression of cyclooxygenase-2( COX-2) and cysteinyl aspartate specific proteinase( Caspase-3) in rat with lung squamous cell carcinoma( LSCC).Methods The SD rats were divided into 4 groups: normal group,model group,low dose and high dose experimental groups according to random number table method,13 rats in each group. Animal models with LSCC were established by bronchial perfusion with 3-methylcholanthrene 6 mg and diethylnitrosamine 8 mg. After successful modeling,the two doses experimental group were given 60 mg·kg~(-1) and 100 mg·kg~(-1) alittinib,respectively. The lesions in the left lobes of rats were taken. The expression of COX-2 and Caspase-3 in lung squamous cell carcinoma was detected by immunohistochemistry. The survival time and life prolongation rate of rats were calculated. Results The survival time in the model group,low dose and high dose experimental groups were( 25. 3 ± 2. 9),( 36. 0 ± 2. 4),( 47. 8 ± 2. 6) d; comparison between two doseexperimental groups and model group,the difference was significant( all P < 0. 05). On the 15 th day of treatment,the expression of COX-2( IOD) in normal group,model group and low and high dose experimental groups were0. 41 ± 0. 14,1. 42 ± 0. 22,0. 97 ± 0. 21 and 0. 76 ± 0. 15,respectively; the expression of Caspase-3 in the four groups were 1. 71 ± 0. 18,0. 56 ± 0. 13,1. 01 ± 0. 16 and 1. 29 ± 0. 19,respectively. Comparison between model group and the normal group,the difference was significant( P < 0. 05); comparison between two dose experimental groups and model group,the difference were significant( all P < 0. 05),and the high dose experimental group was better than the low dose experimental group. Conclusion Aletinib can prolong the survival time of rats with LSCC and improve the quality of life of rats. The reason may be related to the reduction of COX-2 expression and the up-regulation of Caspase-3 expression in LSCC.
Objective To study the effects of alittinib on the expression of cyclooxygenase-2( COX-2) and cysteinyl aspartate specific proteinase( Caspase-3) in rat with lung squamous cell carcinoma( LSCC).Methods The SD rats were divided into 4 groups: normal group,model group,low dose and high dose experimental groups according to random number table method,13 rats in each group. Animal models with LSCC were established by bronchial perfusion with 3-methylcholanthrene 6 mg and diethylnitrosamine 8 mg. After successful modeling,the two doses experimental group were given 60 mg·kg~(-1) and 100 mg·kg~(-1) alittinib,respectively. The lesions in the left lobes of rats were taken. The expression of COX-2 and Caspase-3 in lung squamous cell carcinoma was detected by immunohistochemistry. The survival time and life prolongation rate of rats were calculated. Results The survival time in the model group,low dose and high dose experimental groups were( 25. 3 ± 2. 9),( 36. 0 ± 2. 4),( 47. 8 ± 2. 6) d; comparison between two doseexperimental groups and model group,the difference was significant( all P < 0. 05). On the 15 th day of treatment,the expression of COX-2( IOD) in normal group,model group and low and high dose experimental groups were0. 41 ± 0. 14,1. 42 ± 0. 22,0. 97 ± 0. 21 and 0. 76 ± 0. 15,respectively; the expression of Caspase-3 in the four groups were 1. 71 ± 0. 18,0. 56 ± 0. 13,1. 01 ± 0. 16 and 1. 29 ± 0. 19,respectively. Comparison between model group and the normal group,the difference was significant( P < 0. 05); comparison between two dose experimental groups and model group,the difference were significant( all P < 0. 05),and the high dose experimental group was better than the low dose experimental group. Conclusion Aletinib can prolong the survival time of rats with LSCC and improve the quality of life of rats. The reason may be related to the reduction of COX-2 expression and the up-regulation of Caspase-3 expression in LSCC.
引文
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[10]张黎黎,张洁,张林,等. p53,bcl-2,Caspase-3在老年晚期非小细胞肺癌组织中的表达及对预后的影响[J].北京医学,2014,36(7):581-585.
[2]李韶今,张相民,刘联斌,等. AMPK、NF-κB、COX-2及PGE2在非小细胞肺癌中的表达[J].中国现代医学杂志,2017,27(3):49-54.
[3]林小华,江其生,王思念,等.电离辐射对肺癌A549细胞miR-21体内外表达的影响及意义[J].中华放射学与防护杂志,2018,38(3):168-173.
[4]杨廷桐,方卓宁,张付美,等.大鼠肺鳞癌模型的建立[J].动物医学进展,2009,30(4):27-30.
[5]杨喜花,王俊田,陈丽霞,等.瑞香狼毒提取物对肝癌原位移植瘤小鼠的生命延长作用[J].中国药物与临床,2017,17(4):501-503.
[6]DAHER T,TUR M K,BROBEIL A,et al. Combined human papillomavirus typing and TP53 mutation analysis in distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma[J]. Head Neck,2018,40(6):1109-1119.
[7]陈超,陈慧彬,滕鸣健,等.扶正散结汤拆方对Lewis肺癌移植瘤MVD、HIF-1α及COX-2的影响[J].世界中西医结合杂志,2015,10(4):483-486.
[8]李受南,冼磊,吴正球,等. TCF21与Caspase-3在非小细胞肺癌组织中的表达及意义[J].中国临床新医学,2016,9(4):310-312.
[9]ENOKI E,KIMURA M,YAGUCHI T. Squamous cell carcinoma of the lung associated with non-invasive aspergillosis and localised and peripheral blood eosinophilia[J]. Cytopathol:Official J Br Society Clin Cytol,2017,28(4):347-348.
[10]张黎黎,张洁,张林,等. p53,bcl-2,Caspase-3在老年晚期非小细胞肺癌组织中的表达及对预后的影响[J].北京医学,2014,36(7):581-585.