Abstract 1117: To investigate the effect of fluoxetine combined with radiation therapy on hepatocellular carcinoma

Abstract

Abstract Hepatocellular carcinoma (HCC) is a highly prevalent and lethal primary liver tumor. It commonly occurs in individuals with chronic liver diseases, such as hepatitis B or C related cirrhosis. Despite conventional treatments, such as surgery and chemotherapy, the prognosis for HCC remains poor. The optimal treatment for patients with HCC is contingent on various factors, including the size and location of the tumor, the functional capacity of their liver, and their overall health status. Radiation therapy (RT) is a prevalent cancer treatment modality that targets rapidly dividing tumor cells by utilizing high-energy radiation. It is frequently administered alongside other treatments, such as surgery and chemotherapy, to improve the likelihood of successful cancer management. The timing of RT may vary, as it can be delivered before, during, or after other therapies depending on the patient's specific clinical situation. It's important to note that there are limits to the amount of radiation a patient's body can safely receive over their lifetime. For this reason, RT is often combined with other cancer treatments to enhance its effectiveness in sensitizing HCC cells. Fluoxetine is an anti-depressant drug that has also been shown to inhibit the growth of HCC. However, the potential role of fluoxetine in combination with RT for the treatment of HCC remains uncertain. In this study, we aim to identify whether fluoxetine may sensitize HCC to RT and evaluate its underlying mechanism. In this study, we employed the MTT assay and colon information to assess the cytotoxic effects of fluoxetine and radiotherapy (RT) at varying doses on HCC. Our findings, obtained through flow cytometry, revealed that the combination treatment can elicit extrinsic/intrinsic apoptosis in HCC cells. Specifically, this combination led to the loss of mitochondrial membrane potential, activation of cleaved-caspase-3, -8, -9, Fas, and FasL. Additionally, flow cytometry analysis showed an increase in the activation of PARP-1 and TUNEL, signifying DNA damage induction. Furthermore, we observed that fluoxetine not only enhances this DNA damage but also inhibits DNA repair, as shown through flow cytometry by the suppression of p-ATM and p-CHK2. Our western blotting assay confirmed that fluoxetine effectively inhibits HCC progression by activating LC3B, indicating the induction of autophagy in HCC cells. Moreover, the combined treatment, as demonstrated by transwell and wound healing assays, significantly reduced the migration and invasion capabilities of HCC cells. To conclude, the induction of apoptosis, DNA damage, and autophagy emerges as a crucial mechanism contributing to the heightened sensitivity of HCC cells to RT when combined with Fluoxetine. These results suggest that the combination of Fluoxetine with RT presents a promising novel approach for the treatment of HCC. Citation Format: Bo-Xun Chen, Tsai Lan Liao, Rong-Er Lu, Fei-Ting Hsu, Yuan Chang. To investigate the effect of fluoxetine combined with radiation therapy on hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1117.