A TGFβ Signaling Inhibitor, SB431542, Inhibits Reovirus-mediated Lysis of Human Hepatocellular Carcinoma Cells in a TGFβ-independent Manner

**Background and Aim:** Oncolytic reovirus, a non-enveloped virus with a double-stranded RNA genome composed of 10 segments, is being explored as a new class of antitumor agent. Hepatocellular carcinoma (HCC) has been identified as a promising target for reovirus-based virotherapy. Transforming growth factor (TGF)-β is known to play a crucial role in the development of HCC, and TGF-β signaling inhibitors are currently undergoing clinical trials as potential treatments for HCC. However, TGF-β also promotes the expression of cathepsins B and L, which are key to reovirus infection. It is not yet clear whether TGF-β signaling inhibitors influence the effectiveness of reovirus-induced lysis of HCC cells. This study aimed to assess the impact of TGF-β signaling inhibitors on the efficiency of tumor cell lysis by reovirus in human HCC cells.

**Materials and Methods:** Reovirus was introduced to four human HCC cell lines pretreated with one of three TGF-β type I receptor inhibitors: SB431542, A-83-01, or galunisertib (LY2157299). Following reovirus infection, cell viability, viral genome copy numbers, and viral protein expression were measured.

**Results:** SB431542 was found to significantly reduce the reovirus-mediated killing of human HCC cell lines, whereas A-83-01 and galunisertib did not show this inhibitory effect.

**Conclusion:** These findings suggest that SB431542 inhibits reovirus-induced lysis of human HCC cells through a mechanism that is independent of TGF-β signaling.