SPAG5, the upstream protein of Wnt and the target of curcumin, inhibits hepatocellular carcinoma.

The inhibitory role of curcumin on sperm-associated antigen 5 (SPAG5) and its effects on the cancer‑related Wnt classical signaling pathway has been previously demonstrated. Nevertheless, research on the modulatory role of curcumin on the Wnt signaling pathway by acting on SPAG5 has yet to be reported. The activation of the Wnt/β‑catenin pathway is frequently observed in patients suffering from hepatocellular carcinoma (HCC), suggesting that small molecular drugs that target Wnt could present a promising therapeutic strategy. However, these drugs often result in substantial side effects. In the present study, the presence of SPAG5 in the cancer tissues of patients with HCC and cell lines was validated using immunohistochemistry, cellular immunofluorescence, reverse transcription‑quantitative polymerase chain reaction, and western blot analyses. Subsequently, the effect of SPAG5 and the regulatory role of curcumin on SPAG5 and the Wnt/β‑catenin pathway were examined using cell function tests, flow cytometry, and western blotting. Techniques of gene knockout and overexpression were employed. The findings revealed a significant overexpression of SPAG5 in the cancer tissues of patients with HCC. Both the mRNA and protein levels of SPAG5 in Huh7 and HCCLM3 cell lines were markedly elevated. Treatment with curcumin led to a decrease in SPAG5 expression, while also inhibiting cell migration and promoting apoptosis. Additionally, suppression of SPAG5 expression resulted in the decreased expression of β‑catenin. Furthermore, curcumin was observed to reduce the expression of cyclin D1 in SPAG5‑overexpressing cell lines. However, the degree of inhibition was diminished once SPAG5 expression was silenced. These initial findings indicate that SPAG5 may function as an upstream regulatory protein of the Wnt/β‑catenin pathway, hence offering a potential alternative target for HCC. Moreover, as curcumin has the capacity to inhibit Wnt via suppressing SPAG5, it could potentially serve as a natural drug component for early intervention and treatment of HCC.