A new curcumin analogue with potent suppressive activity in pancreatic cancer

一种新的姜黄素类似物，对胰腺癌具有有效的抑制活性

基本信息

批准号：
7740282
负责人：
Jiayuh Lin
金额：
$ 7.63万
依托单位：
RESEARCH INST NATIONWIDE CHILDREN'S HOSP
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7740282
关键词：
Advanced Malignant Neoplasm Biological Availability Cancer cell line Cell Line Cell Proliferation Cell Survival Cells Chemopreventive Agent Clinical Trials Country Curcumin Diagnosis Dose Drug resistance Excision Exhibits Exocrine pancreas Goals Growth Human In Vitro Individual Intervention Studies Life Localized Disease Malignant Neoplasms Malignant neoplasm of pancreas Modeling Mus Neoplasm Metastasis New Agents Normal Cell Oncogenic Operative Surgical Procedures Pancreatic carcinoma Pathway interactions Patients Phosphorylation Play Proto-Oncogene Proteins c-akt Radiation therapy Role Signal Transduction Staging Stat3 protein Survival Rate Testing Therapeutic Therapeutic Agents Time Toxic effect Tumor Volume United States Xenograft Model analog angiogenesis cancer cell cancer type chemotherapy effective therapy in vivo inhibitor/antagonist innovation lymph nodes mortality mouse model neoplastic cell notch protein novel novel therapeutics outcome forecast overexpression pancreatic neoplasm pre-clinical preclinical study public health relevance response small molecule therapeutic target tumor tumor growth

项目摘要

DESCRIPTION (provided by applicant): Several oncogenic pathways are typical overexpressed and activated in pancreatic cancer, which include AKT, Signal Transducer and Activator of Transcription 3 (STAT3), Notch-1, and NF-?B. An effective therapeutic agent may need to exhibit the capacity to inhibit these pathways. STAT3, Notch-1, NF-?B, and AKT pathways are among the major oncogenic pathways activated in pancreatic cancer. These four oncogenic pathways are considered to play critical roles in growth, survival, invasion, angiogenesis, and other functions in pancreatic cancer and thereby emerged as attractive therapeutic targets for this cancer. We proposed to evaluate the inhibitory efficacy of GO-Y030, a new and more potent analogue of the dietary agent, curcumin. Our preliminary results in this proposal demonstrated for the first time that GO-Y030 is approximately 26-397 times more potent than curcumin in inhibiting pancreatic cancer cell viability as well as more potent than cu cell lines. We will also examine whether the expression of STAT3, AKT, and Notch-1 can rescue the inhibitory effects of GO-Y030 in pancreatic cancer cells. In specific aim 2, we will evaluate the inhibitory efficacy of GO-Y030 to suppress PANC-1, MIA-PACA-2, and BxPC-3 pancreatic cancer cells in orthotopic tumor model. Pancreatic cancer is one of the most serious types of cancer and there is a critical need to develop more effective therapeutic agents for pancreatic cancer. Our proposed studies, if successful, will provide a promising potential using GO-Y030 as a novel therapeutic agent for pancreatic cancer with the ultimate goal to reduce the mortality of pancreatic cancer and extending the quality of healthy life for people in this country and around the world. PUBLIC HEALTH RELEVANCE: Each year about 32,000 individuals in the United States are diagnosed with pancreatic cancer. Cancer of the exocrine pancreas is rarely curable and has an overall survival rate of less than 4%. The. itical need for better treatment approaches for pancreatic cancer. The objectives of this proposal are to evaluate the inhibitory efficacy of a new and highly potent curcumin analogue, GO-Y030 in human pancreatic cancer cells in vitro and in a mouse orthotopic tumor model. These results will provide the pre- clinical activities of GO-Y030 as a potential therapeutic agent for more effective treatment for pancreatic cancer

描述（由申请人提供）：几种致癌途径在胰腺癌中典型地过度表达和激活，其中包括AKT、信号转导子和转录激活子3（STAT3）、Notch-1和NF-κB。有效的治疗剂可能需要表现出抑制这些途径的能力。 STAT3、Notch-1、NF-κB 和 AKT 通路是胰腺癌中激活的主要致癌通路。这四种致癌途径被认为在胰腺癌的生长、存活、侵袭、血管生成和其他功能中发挥着关键作用，因此成为该癌症有吸引力的治疗靶点。我们建议评估 GO-Y030 的抑制功效，GO-Y030 是一种新型且更有效的饮食剂姜黄素类似物。我们在该提案中的初步结果首次证明，GO-Y030 在抑制胰腺癌细胞活力方面比姜黄素强约 26-397 倍，并且比 cu 细胞系更有效。我们还将研究 STAT3、AKT 和 Notch-1 的表达是否可以挽救 GO-Y030 在胰腺癌细胞中的抑制作用。在具体目标2中，我们将评估GO-Y030在原位肿瘤模型中抑制PANC-1、MIA-PACA-2和BxPC-3胰腺癌细胞的抑制功效。胰腺癌是最严重的癌症类型之一，迫切需要开发更有效的胰腺癌治疗药物。我们提出的研究如果成功，将为使用 GO-Y030 作为一种新型胰腺癌治疗剂提供广阔的前景，最终目标是降低胰腺癌的死亡率并提高该国及世界各地人民的健康生活质量世界。公共卫生相关性：美国每年约有 32,000 人被诊断患有胰腺癌。外分泌胰腺癌很少能治愈，总体生存率低于 4%。这。迫切需要更好的胰腺癌治疗方法。该提案的目的是评估新型高效姜黄素类似物 GO-Y030 在体外和小鼠原位肿瘤模型中对人胰腺癌细胞的抑制功效。这些结果将为 GO-Y030 作为潜在治疗剂提供临床前活性，以更有效地治疗胰腺癌