Oncology Department, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
Virology Laboratory, Microbiology Department, The Center of Jinzhou Disease Control and Prevention, Jinzhou, Liaoning 121000, P.R. China.
Mol Med Rep. 2018 Jan;17(1):147-157. doi: 10.3892/mmr.2017.7904. Epub 2017 Oct 26.
Prostate cancer is one of the most common types of malignant tumor of men worldwide and the incidence and mortality rate is gradually increasing. At present, the molecular mechanisms of growth and migration in human prostate cancer have not been completely elucidated. Studies have demonstrated that Ganoderma lucidum polysaccharides (GLP) can inhibit cancer. Therefore the present study investigated the effect and molecular mechanism of GLP on cell growth and migration of LNCaP human prostate cancer cells. LNCaP cells were transfected with either a protein arginine methyltransferase 6 (PRMT6) overexpression plasmid or PRMT6 small interfering (si)RNA. The cell growth and migration, and the expression of PRMT6 signaling‑associated proteins, were investigated following treatment with 5 and 20 µg/ml GLP. The results demonstrated that GLP inhibited cell growth, induced cell cycle arrest, decreased PRMT6, cyclin‑dependent kinase 2 (CDK2), focal adhesion kinase (FAK) and steroid receptor coactivator, (SRC) expression, and increased p21 expression in LNCaP cells, as determined by using a Coulter counter, flow cytometry, and reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. Furthermore, GLP significantly inhibited cell migration, as determined by Transwell migration and scratch assays, and altered CDK2, FAK, SRC and p21 expression in LNCaP cells transfected with the PRMT6 overexpression plasmid. By contrast, PRMT6 knockdown by siRNA reduced the effect of GLP on cell migration. These results indicate that GLP was effective in inhibiting cell growth, the cell cycle and cell migration, and the suppressive effect of GLP on cell migration may occur via the PRMT6 signaling pathway. Therefore, it is suggested that GLP may act as a tumor suppressor with applications in the treatment of prostate cancer. The results of the present study provide both the preliminary theoretical and experimental basis for the investigation of GLP as a therapeutic agent.
前列腺癌是全球男性中最常见的恶性肿瘤之一,其发病率和死亡率逐渐上升。目前,人类前列腺癌生长和迁移的分子机制尚未完全阐明。研究表明,灵芝多糖(GLP)可以抑制癌症。因此,本研究探讨了 GLP 对 LNCaP 人前列腺癌细胞生长和迁移的影响及其分子机制。用蛋白质精氨酸甲基转移酶 6(PRMT6)过表达质粒或 PRMT6 小干扰(si)RNA 转染 LNCaP 细胞。用 5 和 20μg/ml GLP 处理后,研究细胞生长和迁移以及 PRMT6 信号相关蛋白的表达。结果表明,GLP 抑制细胞生长,诱导细胞周期停滞,降低 PRMT6、细胞周期蛋白依赖性激酶 2(CDK2)、黏着斑激酶(FAK)和类固醇受体共激活因子(SRC)的表达,并用库尔特计数器、流式细胞术、逆转录-定量聚合酶链反应和 Western blot 分别测定 p21 表达增加。此外,GLP 显著抑制转染 PRMT6 过表达质粒的 LNCaP 细胞的迁移,通过 Transwell 迁移和划痕试验测定。相反,siRNA 敲低 PRMT6 减少了 GLP 对细胞迁移的影响。这些结果表明,GLP 能有效抑制细胞生长、细胞周期和细胞迁移,GLP 对细胞迁移的抑制作用可能通过 PRMT6 信号通路发生。因此,GLP 可能作为一种肿瘤抑制剂应用于前列腺癌的治疗。本研究为 GLP 作为治疗剂的研究提供了初步的理论和实验依据。