Clinical Medical College of Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China.
Oncol Rep. 2023 Sep;50(3). doi: 10.3892/or.2023.8609. Epub 2023 Aug 4.
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.
姜黄素对精子相关抗原 5（SPAG5）的抑制作用及其对癌症相关 Wnt 经典信号通路的影响已被证实。然而，姜黄素通过作用于 SPAG5 对 Wnt 信号通路的调节作用的研究尚未报道。Wnt/β-连环蛋白通路的激活在患有肝细胞癌（HCC）的患者中经常观察到，这表明针对 Wnt 的小分子药物可能提供一种有前途的治疗策略。然而，这些药物通常会导致严重的副作用。在本研究中，通过免疫组织化学、细胞免疫荧光、逆转录-定量聚合酶链反应和 Western blot 分析验证了 SPAG5 在 HCC 患者的癌组织和细胞系中的存在。随后，使用细胞功能试验、流式细胞术和 Western blot 技术研究了 SPAG5 的作用以及姜黄素对 SPAG5 和 Wnt/β-连环蛋白通路的调节作用。采用基因敲除和过表达技术。研究结果显示，SPAG5 在 HCC 患者的癌组织中表达明显上调。Huh7 和 HCCLM3 细胞系中 SPAG5 的 mRNA 和蛋白水平均显著升高。姜黄素处理导致 SPAG5 表达降低，同时抑制细胞迁移并促进细胞凋亡。此外，抑制 SPAG5 表达导致β-连环蛋白表达降低。此外，观察到姜黄素在过表达 SPAG5 的细胞系中降低了 cyclin D1 的表达。然而，一旦沉默 SPAG5 的表达，抑制程度就会降低。这些初步发现表明，SPAG5 可能作为 Wnt/β-连环蛋白通路的上游调节蛋白发挥作用，因此为 HCC 提供了一个潜在的替代治疗靶点。此外，由于姜黄素能够通过抑制 SPAG5 抑制 Wnt，因此它可能作为 HCC 早期干预和治疗的天然药物成分。
