Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Department of Science and Technology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
J Cancer Res Clin Oncol. 2023 Dec;149(18):16797-16809. doi: 10.1007/s00432-023-05425-3. Epub 2023 Sep 20.
Melanoma is a malignant skin tumor caused by melanocytes and associated with high mortality rates. This study aims to investigate the specific mechanism of ZWZ-3 in melanoma proliferation and metastasis.
RNA sequencing was performed to identify the effect of ZWZ-3 on gene expression. siRNA was used to inhibit BIRC5 gene expression in the B16F10 cell line. A zebrafish tumor model was used to assess the therapeutic effect of ZWZ-3 in vivo. Mechanistic insights into the inhibition of tumor metastasis by ZWZ-3 were obtained through analysis of tumor tissue sections in mice.
Our findings demonstrated that ZWZ-3 suppressed melanoma cell proliferation and migration. We performed RNA sequencing in melanoma cells after the treatment with ZWZ-3 and found that Birc5, which is closely associated with tumor metastasis, was significantly down-regulated. Bioinformatics analysis and the immuno-histochemical results of tissue chips for melanoma further confirmed the high expression of BIRC5 in melanoma and its effect on disease progression. Moreover, Birc5 knock-down significantly inhibited melanoma cell proliferation and metastasis, which was correlated with the β-catenin/HIF-1α/VEGF/MMPs pathway. Additionally, ZWZ-3 significantly inhibited tumor growth in the zebrafish tumor model without any evident side effects. Histological and immuno-histochemical analyses revealed that ZWZ-3 inhibited tumor cell metastasis by down-regulating HIF-1α, VEGF, and MMP9.
Our findings revealed that ZWZ-3 could downregulate BIRC5 and inhibit melanoma proliferation and metastasis through the β-catenin/HIF-1α/VEGF/MMPs pathway. Therefore, BIRC5 represents a promising therapeutic target for the treatment of melanoma.
黑色素瘤是一种由黑色素细胞引起的恶性皮肤肿瘤，死亡率较高。本研究旨在探讨 ZWZ-3 在黑色素瘤增殖和转移中的具体作用机制。
采用 RNA 测序技术研究 ZWZ-3 对基因表达的影响。在 B16F10 细胞系中使用 siRNA 抑制 BIRC5 基因表达。通过建立斑马鱼肿瘤模型评估 ZWZ-3 的体内治疗效果。通过分析小鼠肿瘤组织切片，研究 ZWZ-3 抑制肿瘤转移的机制。
研究发现 ZWZ-3 可抑制黑色素瘤细胞的增殖和迁移。用 ZWZ-3 处理黑色素瘤细胞后进行 RNA 测序，发现与肿瘤转移密切相关的 Birc5 显著下调。生物信息学分析和黑色素瘤组织芯片的免疫组化结果进一步证实了 BIRC5 在黑色素瘤中的高表达及其对疾病进展的影响。此外，Birc5 敲低显著抑制黑色素瘤细胞的增殖和转移，这与β-catenin/HIF-1α/VEGF/MMPs 通路相关。此外，ZWZ-3 在斑马鱼肿瘤模型中显著抑制肿瘤生长，且无明显副作用。组织学和免疫组化分析表明，ZWZ-3 通过下调 HIF-1α、VEGF 和 MMP9 抑制肿瘤细胞转移。
本研究揭示了 ZWZ-3 可通过下调 BIRC5 抑制黑色素瘤的增殖和转移，其作用机制与β-catenin/HIF-1α/VEGF/MMPs 通路有关。因此，BIRC5 可能成为治疗黑色素瘤的一个有前途的治疗靶点。
