Wogonin inhibits radiation-induced DNA damage repair in hepatocellular carcinoma cells by upregulating p21

Wogonin has been shown to exhibit anti-tumor effects by regulating the growth and inducing cell death in hepatocellular carcinoma (HCC) cells. However, its impact on radiotherapy for HCC remains unclear. This study aimed to elucidate the mechanisms and effects of wogonin in enhancing radiotherapy for HCC. The viability and cell cycle of HCC cells were assessed using CCK-8, trypan blue dye exclusion, and flow cytometry. RNA sequencing was performed to explore the genomic effects of wogonin on HCC cells. Immunofluorescence staining was employed to detect γ-H2AX distribution, and Western blot was used to evaluate the expression of γ-H2AX and p21. Wogonin induced cell cycle arrest and inhibited DNA damage repair in SMMC-7721 and HCC-LM3 cells following irradiation. RNA sequencing analysis of wogonin-and radiation-treated cells revealed significant enrichment of genes related to cell cycle progression, with notable changes in CDK inhibitor expression. Furthermore, wogonin in combination with irradiation increased the expression of γ-H2AX and p21 in HCC cells. Notably, p21 interference partially abrogated the anti-tumor effects of wogonin and radiation. Wogonin enhances the efficacy of radiotherapy in HCC by promoting cell cycle arrest and inhibiting DNA damage repair through upregulation of p21.