Bibliographic Details
| Title: |
Olaparib enhancing radiosensitization and anti-metastatic effect of oral cancer by targeting IL-17A signal. |
| Authors: |
Yu, Chih-Chia, Lin, Hon-Yi, Chan, Michael W.Y., Wu, Shu-Fen, Chiou, Wen-Yen, Lee, Moon-Sing, Chi, Chen-Lin, Lin, Ru-Inn, Hsu, Feng-Chun, Yang, Hsuan-Ju, Chen, Liang-Cheng, Chew, Chia-Hui, Hung, Shih-Kai |
| Source: |
Cancer Cell International; 11/11/2024, Vol. 24 Issue 1, p1-13, 13p |
| Subject Terms: |
ANTINEOPLASTIC agents, SQUAMOUS cell carcinoma, IONIZING radiation, OLAPARIB, TUMOR growth |
| Abstract: |
Purpose: We tested whether the PARP inhibitor, Olaparib, can effectively enhance radiosensitivity while inhibiting OSCC growth and metastasis in vitro and in vivo. Patient samples were used for survival validation. Methods: The present study investigated the effect of Olaparib and ionizing radiation (IR) on clonogenic, migratory, and invasive ability in human IR-sensitive (OML1) and IR-resistant (OML1-R) OSCC cell lines. We next explored the underlying mechanism with ELISA and a Western blotting assay. Two in vivo mouse models were established to investigate the efficacy of Olaparib combined with radiotherapy (RT) on local tumor growth and lung metastasis. IL-17 A expression was confirmed in tissue specimens of OSCC patients by immunohistochemistry. Results: We found that Olaparib, in combination with IR, substantially inhibited cell growth, migration, and invasion in vitro. Mechanistically, the Olaparib treatment significantly reduced the secretion of IL-17 A in irradiated OSCC cells by attenuating NF-κB and p38 activity. Consistently, Olaparib enhanced the radiosensitivity and, with RT, synergistically reduced both tumor growth and lung metastasis in mice. In addition, OSCC patients with high IL-17 A expression were substantially associated with an increased risk of lymph node involvement and worse survival. Conclusions: This study has highlighted that Olaparib displays radiosensitizing and antimetastatic effects by inhibiting the IL-17 A-dependent signal. Remarkably, Olaparib could provide a remarkable anticancer efficacy to improve treatment response in OSCC patients with recurrent/metastatic disease after RT. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
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