Molecular mechanism of tissue factor-induced inhibition of apoptosis in lung cancer cells that are resistant to anti-cancer therapy

组织因子诱导抑制抗癌治疗耐药肺癌细胞凋亡的分子机制

基本信息

批准号：
13670597
负责人：
GABAZZA Esteban
金额：
$ 2.3万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Background : Patients with lung cancer are currently treated with a combination of several anti-cancer drugs. However, the occurrence of resistance to chemotherapy generally limits its efficacy in clinical practice. Thus, the mechanism by which resistance to chemotherapy develops is presently the focus of many investigations. So far,-we have demonstrated that the coagulation system plays important role in the pathogenesis of several lung diseases. For example, we have reported that the circulating level of tissue factor is significantly correlated with survival and clinical stage, of patients with lung cancer, and that it is closely associated with the malignant potential of lung cancerAim : In the present investigation we focused on the intracellular pathway associated with tissue factor expression in lung cancer, and evaluated the relationship between the inhibition of apoptosis and resistance to chemotherapy. In addition, we have also assessed the expression, of the inhibitor of fib … More rinolysis, thrombin-activatable fibrinolysis inhibitorMethod : In the experiments, we used highly sensitive lung cancer cell lines (PC/9. PC7/P, PC14/P, H69/P) and those with high resistance to anticancer drug (PC9/CDDP, PC7/CDDP, PC 14/CDDP, H69/CDDP). The expression of tissue factor and thrombin-activatable fibrinolysis inhibitor was evaluated by enzyme-linked immunoassay and reverse transcriptase polymerase chain reactionResults : Lung cancer cell lines with resistance to anticancer drugs showed increased expression of tissue factor compared to sensitive cell lines. By contrast, cell lines with resistance to chemotherapy showed lower expression of thrombin-activatable fibrinolysis inhibitor than those with high sensitivity to cytotoxic drugs. In addition, the intracellular apoptotic pathway was inhibited in resistant lung cancer cells but not in sensitive cellsConclusion : These results suggest that both tissue factor,and thrombin-activatable fibrinolysis inhibitor are involved in the mechanism of resistance to chemotherapy in lung cancer. Tissue factor and thrombin-activatable fibrinolysis inhibitor may constitute potential indicator of resistance to chemotherapy in patients with lung cancer Less

背景：肺癌患者目前已通过几种抗癌药物的组合治疗。但是，对化学疗法的抗性的发生通常会限制其在临床实践中的有效性。这是许多研究的重点，这是对化学疗法发展的机制。到目前为止，我们已经证明，凝结系统在几种肺部疾病的发病机理中起重要作用。例如，我们报告说，组织因子的循环水平与肺癌患者的存活和临床阶段显着相关，并且与肺癌的恶性潜力密切相关：在介绍研究中，我们集中于与肺癌中与组织因子的胞内途径相关的细胞内途径，并评估了抑制型和抑制性的抑制作用和抑制作用之间的关系。 In addition, we have also assessed the expression, of the Inhibitor of fib … More rinolysis, thrombin-activatable fibrinolysis inhibitorMethod : In the experiments, we used highly sensitive lung cancer cell lines (PC/9. PC7/P, PC14/P, H69/P) and those with high resistance to anticancer drug (PC9/CDDP, PC7/CDDP, PC 14/CDDP, H69/CDDP）。通过酶联免疫测定和逆转录酶聚合酶链反应反应评估组织因子和凝血酶激活的纤维蛋白溶解抑制剂的表达：与敏感细胞系相比，组织因抗癌药物的抗性增加，表现出对抗癌药物的抗性增加。相比之下，对化学疗法的耐药性的细胞系表明，与细胞毒性药物敏感的抑制剂相比，凝血酶激活的纤维蛋白溶解抑制剂的表达较低。此外，在耐药性肺癌细胞中抑制细胞内凋亡途径，但在敏感的细胞结缝中不抑制：这些结果表明，组织因子和凝血酶激活的纤维蛋白解抑制剂均参与肺癌化学疗法的抗性机制。组织因子和凝血酶激活的纤维蛋白解抑制剂可能构成潜在的肺癌患者化学疗法的指标。