Modulation of PI3K/AKT Signaling related Apoptosis Protein enhanced Radio Sensitivity of Human Cancer Cells

• Main Authors: Szu-Yuan Wu, 吳思遠
• Other Authors: 劉興華
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/34pku9

博士 === 國立臺灣大學 === 毒理學研究所 === 105 === Radiotherapy is one of the main therapies for cancers in the world. However, radioresistance is still difficultly resolved in radiotherapy. To evaluate the primary pathway to enhance radiation effect in cancer treatment, we analyses some radioresistance cancers with radiotherapy. Initially we found the effects of fucoidan led to inhibition of epithelial-mesenchymal transition in breast cancer cells by an activation of phosphoinositide 3-kinase (PI3K)/Akt pathway. Fucoidan inhibit the progression of breast cancer cells through regulating the miR-29c/ADAM12 and miR-17-5p/PTEN axes. Furthermore, miR-17-5p AS ODN was used to evaluate the in vitro and in vivo radiosensitization effect. Our further study revealed that the enhancement of p53 expression significantly enhanced the radiation-induced G2/M arrest of the OC3 cells (betel nut chewing induced radioresistence buccal cancer cell line). In the in vivo study, treatment with miR-17-5p AS ODN before irradiation significantly enhanced p53 expression and reduced tumor growth. These results revealed that miR-17-5p regulates apoptosis-related proteins in irradiated OC3 cells; its effect on p53 protein expression contributes to the modulation of the radiosensitivity of the OC3 cells. Finally, we evaluated the effects of combining the EGFR inhibition and radiation on PC-3 prostate cancer cells (androgen-independent). By using a apaptosis protein array, we found that several apaptosis related protein (Catalase, cIAP-1, Clusterin, Fas, HIF-1α, HSP27, HSP60, HSP70, SMAC and Survivin) were significantly downregulated in radiation and ERBITUX combined group. Our results demonstrated that Erbitux enhanced apoptosis effects of radiation on PC-3 through down-regulation of PI3K/AKT Signaling. Taken together, modulation of PI3K/AKT signaling related apoptosis protein enhanced radio sensitivity of human cancer cells.