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：
7874486
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 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7874486
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过表达和激活，其中包括AKT，信号换能器和转录3（STAT3），Notch-1和NF-？b。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-？B和AKT途径是胰腺癌激活的主要致癌途径之一。这四种致癌途径被认为在胰腺癌的生长，生存，侵袭，血管生成和其他功能中起着至关重要的作用，从而成为该癌症的有吸引力的治疗靶标。我们建议评估GO-Y030的抑制功效，GO-Y030是饮食剂姜黄素的一种新的，更有效的类似物。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的效力大约是姜黄素的26-397倍，并且比CU细胞系更有效。我们还将检查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。在特定目标2中，我们将评估GO-Y030抑制Panc-1，Mia-Paca-2和BXPC-3胰腺癌细胞中的抑制作用。胰腺癌是最严重的癌症类型之一，对于为胰腺癌开发更有效的治疗剂的迫切需要。如果成功的话，我们提出的研究将使用GO-Y030作为胰腺癌的新型治疗剂，以降低胰腺癌死亡率并扩大该国和世界各地的人们健康生活的质量的最终目标。公共卫生相关性：美国每年约有32,000名诊断出患有胰腺癌。外分泌胰腺癌很少可以治愈，总生存率低于4％。这。对胰腺癌的更好治疗方法的意义。该提案的目标是评估一种新的且高度有效的姜黄素类似物的抑制作用，在人类胰腺癌细胞中GO-Y030在体外和小鼠的矫形型肿瘤模型中。这些结果将提供GO-Y030作为胰腺癌治疗更有效治疗的潜在治疗剂的临床活动