Radiation Biology

PV QA 1 - Poster Viewing Q&A 1

SU_36_2365 - Targeting inhibition of EGFR nuclear nuclear transport sensitizes cervical cancer cells to ionizing radiation

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Targeting inhibition of EGFR nuclear nuclear transport sensitizes cervical cancer cells to ionizing radiation
J. Lang1, L. Li2, J. M. Huang1, M. Feng3, Y. X. Qi1, and X. Lai1; 1Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, chengdu, China, 2Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China, 3#55, Section 4, Renmin South Road, #55, Section 4, Renmin South Road, China

Purpose/Objective(s): EGFR nuclear transport has been proposed to mediate DNA-PK activation for NHEJ repair of DNA damage of cancer cells exposed to ionizing radiation. We examed whether inhibition of radiation-induced expression of pEGFRThr654 and pDNA-PKThr2609 improves the radiation response of cervical cancer cells.

Materials/Methods: Expression of mEGFR and pEGFRThr654 was evaluated by immunohistochemistry and survival analysis in 90 tumor biopsies of cervical cancer patients; Expression of mEGFR,pEGFRThr654, DNA-PK and pDNA-PKThr2609 in the cytoplasm and nuclei of Ca-Ski and HeLa cells X-irradiated (6MV ) with a single dose of 4Gy combining pEGFRThr654 inhibitory peptide,Cetuximab or Gefitinib was determined using Western blot, and also cell radiation survival fraction was determined using a colony-forming assay.

Results: High stainings of mEGFR and pEGFRThr654 were found in 44 (48.9%) and 43 (47.8%) of 90 patients with cervical cancer. In multivariate analysis, pEGFRThr654 was an independent factor for poor PFS (P=0.006) and OS (P=0.008). Expression of pEGFRThr654 and pDNA-PKThr2609 in the nuclei of CaSki and HeLa cells after irradiation were up-regulated in a time-dependent manner, as compared to that without irradiation; pEGFRThr654 inhibitory peptide and Cetuximab significantly declined the expression of pEGFRThr654 and pDNA-PKThr2609 of CaSki and HeLa cells as well as the control A431 cell; Cetuximab or Gefitinib in combination with irradiation remarkably reduced the survival fraction of CaSki and HeLa cells.

Conclusion: Targeting inhibition of pEGFRThr654 nuclear transport-mediated activation of DNA-PK sensitizes cervical cancer cells to ionizing radiation, and Cetuximab in combination with radiotherapy could potentiate the therapeutic gain for cervical cancer.

Author Disclosure: J. Lang: None. L. Li: None. J.M. Huang: None. X. Lai: None.

Jinyi Lang, MD, PhD

Disclosure:
Employment
Si Chuan Cancer Hospital and Institution: Professor: Employee

Presentation(s):

Send Email for Jinyi Lang


Assets

SU_36_2365 - Targeting inhibition of EGFR nuclear nuclear transport sensitizes cervical cancer cells to ionizing radiation



Attendees who have favorited this

Please enter your access key

The asset you are trying to access is locked. Please enter your access key to unlock.

Send Email for Targeting inhibition of EGFR nuclear nuclear transport sensitizes cervical cancer cells to ionizing radiation