In vivo study of breast carcinoma radiosensitization by targeting eIF4E

• Published in: Biochemical and biophysical research communications 2012-07, Vol.423 (4), p.878-883
• Main Authors: Yang, Hua, Li, Li-Wen, Shi, Mei, Wang, Jian-Hua, Xiao, Feng, Zhou, Bin, Diao, Li-Qiong, Long, Xiao-Li, Liu, Xiao-Li, Xu, Lin
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; APOPTOSIS; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast Neoplasms - radiotherapy; CARCINOMAS; Carrier Proteins - genetics; Cell Line, Tumor; Down-Regulation; eIF4E; Eukaryotic Initiation Factor-4E - antagonists & inhibitors; Eukaryotic Initiation Factor-4E - metabolism; Female; Genetic Therapy - methods; Genetic Vectors; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; IN VIVO; INHIBITION; IRRADIATION; MAMMARY GLANDS; MICE; Mice, Inbred BALB C; Phosphoproteins - genetics; pSecX-t4EBP1; Radiation Tolerance; RADIOSENSITIVITY; Radiosensitization; Tumor Burden; TUMOR CELLS; Xenograft; Xenograft Model Antitumor Assays
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2012.06.064

► eIF4E is associated with the formation and progression for breast cancer. ► pSecX-t4EBP1 can downregulated the expression of eIF4E in direct binding. ► We transfected pSecX-t4EBP1 into a mouse xenograft model. ► It can significantly inhibit tumor growth and enhance the radiosensitivity. ► The possible mechanism is downregulation of HIF-1α expression. Eukaryotic initiation factor eIF4E, an important regulator of translation, plays a crucial role in the malignant transformation, progression and radioresistance of many human solid tumors. The overexpression of this gene has been associated with tumor formation in a wide range of human malignancies, including breast cancer. In the present study, we attempted to explore the use of eIF4E as a therapeutic target to enhance radiosensitivity for breast carcinomas in a xenograft BALB/C mice model. Ninety female BALB/C mice transfected with EMT-6 cells were randomly divided into six groups: control, irradiation (IR), pSecX-t4EBP1, pSecX-t4EBP1+irradiation, pSecX and pSecX+irradiation. At the end of the experiments, all mice were sacrificed, the xenografts were harvested to measure the tumor volume and mass, and the tumor inhibition rates were calculated. Apoptosis was detected with a flow cytometric assay. Immunohistochemistry was used to detect the expression of HIF-1α. The xenografts in pSecX-t4EBP1 mice showed a significantly delayed growth and smaller tumor volume, with a higher tumor inhibition rate compared with the control and pSecX groups. A similar result was obtained in the pSecX-t4EBP1+IR group compared with IR alone and pSecX+irradiation. The expression of HIF-1α in the tumor cells was significantly decreased, while the apoptosis index was much higher. pSecX-t4EBP1 can significantly inhibit tumor growth and enhance the radiosensitivity of breast carcinoma xenografts in BALB/C mice. This is possibly associated with the downregulation of HIF-1α expression, which suggests that pSecX-t4EBP1 may serve as an ideal molecular target for the radiosensitization of breast carcinoma.