Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.
Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, P. R. China.
Prostate. 2023 Nov;83(15):1430-1445. doi: 10.1002/pros.24605. Epub 2023 Jul 30.
Melittin is a small molecule polypeptide extracted from the abdominal cavity of bees, which is used to treat inflammatory diseases and relieve pain. However, the antitumor effect of melittin and its mechanisms remain unclear, especially in castration-resistant prostate cancer (CRPC).
Through CCK-8 assay, colony formation assay, wound healing assay and Transwell migration assay, we explored the effect of melittin on CRPC cell lines. In addition, with microarray analysis, gene ontology analysis and kyoto encyclopedia of genes and genomes analysis, this study identified key genes and signaling pathways that influence the growth of PC-3 cells. Meanwhile, the effect of melittin on CRPC was also verified through subcutaneous tumor formation experiments. Finally, we also tested the relevant indicators of human prostate cancer (PCa) specimens through immunohistochemistry and H＆E stating.
Here, melittin was verified to inhibit the cell proliferation and migration of CPRC. Moreover, RNA-sequence analysis demonstrated that Interleukin-17 (IL-17) signaling pathway gene Lipocalin-2 (LCN2) was downregulated by melittin treatment in CRPC. Further investigation revealed that overexpression of LCN2 was able to rescue tumor suppression and cisplatin sensitivity which melittin mediated. Interestingly, the expression of LCN2 is highly related to metastasis in PCa.
In brief, our study indicates that LCN2 plays an oncogenic role in CRPC and melittin may be selected as an attractive candidate for CRPC therapy.
蜂毒素是从小蜜蜂腹部提取的一种小分子多肽，用于治疗炎症性疾病和缓解疼痛。然而，蜂毒素的抗肿瘤作用及其机制尚不清楚，尤其是在去势抵抗性前列腺癌（CRPC）中。
通过 CCK-8 检测、集落形成实验、划痕愈合实验和 Transwell 迁移实验，我们研究了蜂毒素对 CRPC 细胞系的影响。此外，通过微阵列分析、基因本体分析和京都基因与基因组百科全书分析，确定了影响 PC-3 细胞生长的关键基因和信号通路。同时，还通过皮下肿瘤形成实验验证了蜂毒素对 CRPC 的作用。最后，我们还通过免疫组织化学和 H＆E 染色检测了人前列腺癌（PCa）标本的相关指标。
蜂毒素被证实可抑制 CRPC 的细胞增殖和迁移。此外，RNA 测序分析表明，蜂毒素处理后，白细胞介素 17（IL-17）信号通路基因脂联素 2（LCN2）在 CRPC 中下调。进一步研究表明，LCN2 的过表达能够挽救蜂毒素介导的肿瘤抑制和顺铂敏感性。有趣的是，LCN2 的表达与 PCa 的转移高度相关。
总之，我们的研究表明，LCN2 在 CRPC 中发挥致癌作用，蜂毒素可能被选为 CRPC 治疗的有吸引力的候选药物。
