- 作者: Young-Chau Liu b,d, Chuen-Miin Leu b, Fen-Hwa Wong c, Wan-Shung Fong a, Shan-Chun Chen b, Chungming Chang a,b, Cheng-po Hu a,b
- 作者服務機構: a Department of Medical Research and Education , Veterans General Hospital-Taipei , b lIstitute of Microbiology and Immunology, c Institute of Public Health , National Yang-Ming University , Taipei , d College of Liberal Education Shu-Te University , Kaohsiung , Taiwan , ROC
- 中文摘要: --
- 英文摘要: Insulin-like growth factor I (IGF-I) receptor (IGF-IR)-me-diated signals are known to be involved in cell growthand transformation and prevention of apoptosis. In thisstudy, we demonstrated the coexpression of IGF-I andIGF-IR in human esophageal carcinoma tissues. We alsodemonstrated the IGF-I autocrine system in esophagealcarcinoma cell lines. Both the CE48T/VGH and CE81T/VGH cell lines showed proliferative responses to IGF-Istimulation. Autokinase activity of IGF-IR in these cellscan be triggered by the exogenous addition of IGF-l. Inaddition, an IGF-l peptide antagonist, JB1, specificallyinhibited ligand-induced receptor autophosphorylationin a dose-dependent manner. Under serum-free condi-tions, JB1 also reduced the degree of IGF-IR phosphory-lation and cell numbers. Furthermore, the addition ofJB1 decreased the number of CE81T/VGH coloniesformed in methyl cellulose agar and the size and the inci-dence of tumors which grew in mice with severe com-bined immunodeficiency. These results imply that anIGF-I autocrine system in human esophageal carcinomacells could stimulate tumor growth. Finally, we foundthat IGF-I prevented the apoptosis of CE81T/VGH cellsinduced by chemotherapeutic drugs, such as cisplatin,5-fluorouracil and camptothecin. Thus, interruption ofIGF-IR function may provide a way to retard tumorgrowth and increase the sensitivity of esophageal carci-noma to chemotherapy.
- 中文關鍵字: --
- 英文關鍵字: Insulin-like growth factorl, Esophagus, Carcinoma, Tumorigenicity, Chemotherapy