To study the expression of cyclooxygenase 2 (COX-2) gene and its relationship with clinicopathological characteristics of lung cancer, expression of the COX-2 mRNA was evaluated by reverse transcription polymerase ch...To study the expression of cyclooxygenase 2 (COX-2) gene and its relationship with clinicopathological characteristics of lung cancer, expression of the COX-2 mRNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in cancerous tissues and paired adjacent non-cancerous tissues from 56 patients and benign lesions from 12 patients. Our results showed that expression of COX-2 gene was detected in a significantly greater proportion of cancerous tissues (60.7 %) than adjacent noncancerous tissues (10.7 %, P<0.01) and benign lesions (3/12, P<0.05). Expression of COX-2 gene was higher in adenocarcinoma than in squamous carcinoma (P<0.01). There was no significant relationship between COX-2 gene expression and patients' age, sex, histological type of tumors, differentiation degree and TNM stages (P>0.05). The up-regulation of COX-2 gene in lung cancer tissues especially in adenocarcinoma suggested that COX-2 may play a role in the lung carcinogenesis and COX-2 gene may serve as a potential therapeutic target in lung cancer.展开更多
Background Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro,in animal models,and in human clinical trials.The antitumor effect of selective cyclooxy...Background Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro,in animal models,and in human clinical trials.The antitumor effect of selective cyclooxygenase(COX)-2 inhibitors has been demonstrated in preclinical studies.However,no information is available on the effects of p53 gene therapy combined with selective COX-2 inhibitor on COX-2 gene expression and growth inhibition of human lung cancer cells.Methods We evaluated the effects of recombinant adenovirus-p53(Ad-p53) gene therapy combined with selective COX-2 inhibitor on the proliferation,apoptosis,cell cycle arrest of human lung adenocarcinoma A549 cell line,and the effects of tumor suppressor exogenous wild type p53 on COX-2 gene expression.ResultsAd-p53 gene therapy combined with selective COX-2 inhibitor celecoxib shows significant synergistic inhibition effects on the growth of human lung adenocarcinoma A549 cell line. Exogenous p53 gene can suppress COX-2 gene expression.ConclusionsSignificant synergistic inhibition effects of A549 cell line by the combined Ad-p53 and selective COX-2 inhibitor celecoxib may be achieved by enhancement of growth inhibition,apoptosis induction and suppression of COX-2 gene expression.This study provides first evidence that the administration of p53 gene therapy in combination with COX-2 inhibitors might be a new clinical strategy for the treatment or prevention of NSCLC.展开更多
In order to investigate the expression of cyclooxygenase-2 (COX-2) in human lower segments of myometrium obtained from women in labor and those not in labor and identify the splicing variant of COX-2, reverse transcri...In order to investigate the expression of cyclooxygenase-2 (COX-2) in human lower segments of myometrium obtained from women in labor and those not in labor and identify the splicing variant of COX-2, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of COX-2. The primers were designed and synthesized according to the sequence of rat COX-2 splice variant which was discovered firstly by us. Then the splicing variant of COX-2 in human myometrium from woman in labor was identified, cloned into vector and sequenced. The results showed that the expression of COX-2 mRNA was lower in human myometrium obtained from women who were not in labor than that in labor women and a new band of COX-2 was obtained in myometrium from labor woman. The fragment included an unspliced intron, which pitched between exons 7 and 8. It was suggested that COX-2 gene was not only expressed highly in human myometrium from woman in labor, but also produced splicing variant by alternative splicing.展开更多
目的应用网络药理学方法探究川芎-当归药对的主要活性成分、靶点和药理作用机制。方法研究时间为2020年9—12月。首先以“川芎”“当归”为关键词,在TCMSP 2.3数据库中检索药材的成分、靶点和对应疾病数据,构建“药物-成分靶点-疾病”网...目的应用网络药理学方法探究川芎-当归药对的主要活性成分、靶点和药理作用机制。方法研究时间为2020年9—12月。首先以“川芎”“当归”为关键词,在TCMSP 2.3数据库中检索药材的成分、靶点和对应疾病数据,构建“药物-成分靶点-疾病”网络,进行基因本体(gene ontology,GO)分类富集分析、京都基因和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,探究“川芎-当归”药对作用机制。结果“药物-成分-靶点-疾病”网络包含2个药物、10个活性成分,71个作用靶点,191种疾病。关键靶点涉及环氧化酶2(PTGS2)、过氧化物酶体增生激活受体γ(PPARG)、雌激素受体(ESR1)、β2肾上腺素能受体(ADRB2)、周期蛋白依赖激酶2(CDK2)、热休克蛋白90(HSP90)、促分裂原活化蛋白激酶14(MAPK14)、胆碱能受体2(CHRM2)、5羟色胺受体2A(HTR2A)、凝血因子Ⅱ受体(F2R)、盐皮质激素受体(NR3C2)、内皮型一氧化氮合酶(NOS3)等,关键疾病涉及疼痛、心血管疾病、乳腺癌、阿尔茨海默病、炎症、癌症、焦虑症、精神分裂症、前列腺癌、实体肿瘤、脑损伤等。GO富集分析得到237个条目,包括生物过程178个,分子功能26个,细胞组成33个。通路富集分析包含66条通路,主要涉及神经活性配体-受体相互作用、钙离子信号通道、癌症通路、5-羟色胺能突触、大肠癌、雌激素信号通路、心肌细胞的肾上腺素能信号、甲状腺激素信号通路、cAMP信号通路、血管内皮生长因子信号通路等。结论“川芎-当归”药对中多个成分作用于多个靶点和通路,对疼痛、心血管疾病、乳腺癌、阿尔茨海默病、炎症、癌症等多种疾病均一定的治疗作用。展开更多
文摘To study the expression of cyclooxygenase 2 (COX-2) gene and its relationship with clinicopathological characteristics of lung cancer, expression of the COX-2 mRNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in cancerous tissues and paired adjacent non-cancerous tissues from 56 patients and benign lesions from 12 patients. Our results showed that expression of COX-2 gene was detected in a significantly greater proportion of cancerous tissues (60.7 %) than adjacent noncancerous tissues (10.7 %, P<0.01) and benign lesions (3/12, P<0.05). Expression of COX-2 gene was higher in adenocarcinoma than in squamous carcinoma (P<0.01). There was no significant relationship between COX-2 gene expression and patients' age, sex, histological type of tumors, differentiation degree and TNM stages (P>0.05). The up-regulation of COX-2 gene in lung cancer tissues especially in adenocarcinoma suggested that COX-2 may play a role in the lung carcinogenesis and COX-2 gene may serve as a potential therapeutic target in lung cancer.
文摘Background Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro,in animal models,and in human clinical trials.The antitumor effect of selective cyclooxygenase(COX)-2 inhibitors has been demonstrated in preclinical studies.However,no information is available on the effects of p53 gene therapy combined with selective COX-2 inhibitor on COX-2 gene expression and growth inhibition of human lung cancer cells.Methods We evaluated the effects of recombinant adenovirus-p53(Ad-p53) gene therapy combined with selective COX-2 inhibitor on the proliferation,apoptosis,cell cycle arrest of human lung adenocarcinoma A549 cell line,and the effects of tumor suppressor exogenous wild type p53 on COX-2 gene expression.ResultsAd-p53 gene therapy combined with selective COX-2 inhibitor celecoxib shows significant synergistic inhibition effects on the growth of human lung adenocarcinoma A549 cell line. Exogenous p53 gene can suppress COX-2 gene expression.ConclusionsSignificant synergistic inhibition effects of A549 cell line by the combined Ad-p53 and selective COX-2 inhibitor celecoxib may be achieved by enhancement of growth inhibition,apoptosis induction and suppression of COX-2 gene expression.This study provides first evidence that the administration of p53 gene therapy in combination with COX-2 inhibitors might be a new clinical strategy for the treatment or prevention of NSCLC.
基金This project was supported by grants from National Natu ral Sciences Foundation of China ( No. 30070929,30271363).
文摘In order to investigate the expression of cyclooxygenase-2 (COX-2) in human lower segments of myometrium obtained from women in labor and those not in labor and identify the splicing variant of COX-2, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of COX-2. The primers were designed and synthesized according to the sequence of rat COX-2 splice variant which was discovered firstly by us. Then the splicing variant of COX-2 in human myometrium from woman in labor was identified, cloned into vector and sequenced. The results showed that the expression of COX-2 mRNA was lower in human myometrium obtained from women who were not in labor than that in labor women and a new band of COX-2 was obtained in myometrium from labor woman. The fragment included an unspliced intron, which pitched between exons 7 and 8. It was suggested that COX-2 gene was not only expressed highly in human myometrium from woman in labor, but also produced splicing variant by alternative splicing.
文摘目的应用网络药理学方法探究川芎-当归药对的主要活性成分、靶点和药理作用机制。方法研究时间为2020年9—12月。首先以“川芎”“当归”为关键词,在TCMSP 2.3数据库中检索药材的成分、靶点和对应疾病数据,构建“药物-成分靶点-疾病”网络,进行基因本体(gene ontology,GO)分类富集分析、京都基因和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,探究“川芎-当归”药对作用机制。结果“药物-成分-靶点-疾病”网络包含2个药物、10个活性成分,71个作用靶点,191种疾病。关键靶点涉及环氧化酶2(PTGS2)、过氧化物酶体增生激活受体γ(PPARG)、雌激素受体(ESR1)、β2肾上腺素能受体(ADRB2)、周期蛋白依赖激酶2(CDK2)、热休克蛋白90(HSP90)、促分裂原活化蛋白激酶14(MAPK14)、胆碱能受体2(CHRM2)、5羟色胺受体2A(HTR2A)、凝血因子Ⅱ受体(F2R)、盐皮质激素受体(NR3C2)、内皮型一氧化氮合酶(NOS3)等,关键疾病涉及疼痛、心血管疾病、乳腺癌、阿尔茨海默病、炎症、癌症、焦虑症、精神分裂症、前列腺癌、实体肿瘤、脑损伤等。GO富集分析得到237个条目,包括生物过程178个,分子功能26个,细胞组成33个。通路富集分析包含66条通路,主要涉及神经活性配体-受体相互作用、钙离子信号通道、癌症通路、5-羟色胺能突触、大肠癌、雌激素信号通路、心肌细胞的肾上腺素能信号、甲状腺激素信号通路、cAMP信号通路、血管内皮生长因子信号通路等。结论“川芎-当归”药对中多个成分作用于多个靶点和通路,对疼痛、心血管疾病、乳腺癌、阿尔茨海默病、炎症、癌症等多种疾病均一定的治疗作用。
