Abstract 2409: A synergistic effect of miR-21-5p inhibitor and PARP1 inhibitor to enhance the radiosensitivity of oral squamous cell carcinoma

Abstract

Abstract Radiotherapy is one of the standard treatments for oral squamous cell carcinoma (OSCC). Radiotherapy damages cancer cells mainly by inducing DNA double-strand breaks, but some advanced OSCC can effectively repair DNA damages, resulting in radiotherapy resistance. TCGA data showed that miR-21-5p was highly expressed in advanced OSCC and correlated with prognosis. However, the involvement of miR-21-5p in OSCC’s response to radiotherapy and the underlying mechanism are still unclear. When treated with a miR-21-5p inhibitor, we found OSCC cell lines (SAS and CAL33) became more sensitive to X-ray radiation at 2Gy (the commonly used single-dose in conventional radiotherapy), which was supported by the evidence that more resident 53BP1-marked-foci for non-repaired DNA double strand breaks (1.61±0.54 folder more in SAS, 1.47±0.49 folder more in CAL33, n=4, p<0.05) and less colony-forming capacity (14.62±2.36% in SAS, 18.65±4.32% in CAL33, n=3, p<0.05) than untreated control cells were observed at 24hr after radiation. However, the expression of PARP1, a DNA damage sensor for recognizing DNA damage and facilitating DNA repair, was significantly increased (1.38±0.12, n=4, p<0.05) in SAS cells treated with miR-21-5p inhibitor. In order to achieve a better tumor control, we tested the combined treatments with miR-21-5p inhibitor and PARP1 inhibitor (Olaparib) on SAS cells, which resulted in a synergistic effect in inhibition of the repair of DNA double strand breaks. The residual 53BP1 foci after 2Gy X-ray irradiation was increased 1.45±0.06 folder more when inhibiting both miR-21-5p and PARP1, while the colony-forming capacity of irradiated SAS cells was decreased by 39.55±5.89% (p<0.0001) in the same conditions. This work provided novel insights on the molecular mechanism of miR-21-5p regulated cell response to radiotherapy, which may give rise to potential therapeutic strategy for treatment of advanced OSCC. Citation Format: Lin Ma, Weitao Hu, Rui Fu, Anhui Wu, Qiangyong Deng, Qi Liu. A synergistic effect of miR-21-5p inhibitor and PARP1 inhibitor to enhance the radiosensitivity of oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2409.