The Role of TIAF1 in Paclitaxel-induced Cell Cycle Arrest in Glioblastoma

  • 張 欣慈

Student thesis: Master's Thesis

Abstract

Glioblastoma (GBM) is one of most difficult to treat tumors due to its invasiveness and low sensitivity to radiotherapy and chemotherapy The expression of transforming growth factor β 1-induced anti-apoptotic factor 1 (TIAF1) is upregulated in the developing tumor and proliferating GBM GBM is frequently resistant to radiotherapy or chemotherapy In order to study the potential role of TIAF1 in tumor growth under the stress We used the anticancer drug Paclitaxel (Taxol) to arrest the cell cycle in GBM cells We were investigated the role of TIAF1 in paclitaxel-induced cell cycle arrest in Glioblastoma TIAF1 is a downstream effector of the Transforming growth factor β (TGF-β) We used the MTT assay flow cytometry immunocytochemistry bromodeoxyuridine (BrdU) incorporation assay and Western blot to examine the cell viability cell cycle distribution proliferation and cell cycle related proteins following Taxol and/or TGF-β1 treatment in rat GBM CNS-1 and human GBM 1306-MG cells Our data showed that TGF-β1 allow cells to leave G0/G1 phase and enter S and G2/M phase under the 100nM Taxol treatment for 36 hours in CNS-1 cells The TGF-β1 was via upregulated cell cycle related proteins cyclin A cdc25C and cyclin B1 in CNS-1 cells under the 100nM Taxol treatment for 24 hours In CNS-1 cells TGF-β1 also induced G2/M phase arrest under 500nM Taxol treatment for 48 hours The TGF-β1 was via upregulated cell cycle related proteins p53 cdc25C cyclin B1 and CDK1 in CNS-1 cells under the 500nM Taxol treatment for 24 or 36 hours In 1306-MG cells TGF-β1 allows more cells leave G1 phase under the Taxol treatment for 36 hours The TGF-β1 was via upregulated cell cycle related cyclin E in 1306-MG cells under the Taxol treatment for 24 and 36 hours Then we transfected the TIAF1 plasmid DNA into GBM cells Our data showed that TIAF1 downregulated subG1 and S phase and arrested CNS-1 cells in G2/M phase following 100 or 500 nM Taxol treatment In 1306-MG cells TIAF1 arrested cells in G0/G1 phase and inhibited cells division following 100 or 500 nM Taxol treatment In conclusion our findings indicate that the role of TGF-β1 in Taxol induce cell cycle arrest may through upregulated cyclin A cdc25C and cyclin B to induce G0/G1 phase downregulation or through upregulated p53 cdc25C cyclin B and CDK1 to induced G2/M phase arrest in CNS-1 cells The role of TGF-β1 in Taxol induce cell cycle arrest may through upregulated cyclinE to induce G0/G1 phase downregulation in 1306-MG cells Then TIAF1 in Taxol-induced cell cycle arrest may downregulate subG1 and S phase and induced G2/M arrest in CNS-1 cells In 1306-MG cells the role of TIAF1 in Taxol induces cell cycle arrest may downregulate G0/G1 phase and inhibite the cells division
Date of Award2015 Feb 11
Original languageEnglish
SupervisorChun-I Sze (Supervisor)

Cite this

The Role of TIAF1 in Paclitaxel-induced Cell Cycle Arrest in Glioblastoma
欣慈, 張. (Author). 2015 Feb 11

Student thesis: Master's Thesis