Shihezi University School of Medicine, Bei-Er-Lu, Shihezi, 832000, Xinjiang, China.
Institute of Clinical Medicine, Zhanjiang Central People's Hospital, Zhanjiang, 524045, China.
BMC Cancer. 2023 May 11;23(1):426. doi: 10.1186/s12885-023-10841-2.
In previous study, we found that the content of medium-chain fatty acid Caprylic Acid (FFA C8:0) may be an important risk factor of obesity induced prostate cancer (PCa). However, the relationship between FFA C8:0 and PCa has not been reported. In this study, we explored whether the FFA C8:0 can promotes the progression of PCa by up-regulating Krüppel-like factor 7 (KLF7).
We collected tissues from PCa patients and Benign Prostate Hyperplasia (BPH), constructed a primary-tumor bearing mouse model with obesity through high-fat diet, and observed the tumor formation ability of PCa cells. In vitro, CCK8 assay, plate cloning, Transwell and scratch experiment were used to detect the changes in biological behavior of PCa cells stimulated by FFA C8:0.
First, we found that the expression level of KLF7 is higher in PCa tissues of patients, and the expression of KLF7 is positively correlated with tumour-promoting gene IL-6, while it is negative correlated with another tumour-suppressor gene p21. Then, this study found that PCa cells were more likely to form tumors in diet induced obese mice. Compared with the normal diet group (ND), the expression levels of KLF7 in tumor tissues in high-fat diet group (HFD) were higher. Futhermore, we verified that high concentrations of FFA C8:0 can promote the biological behavior of PCa cells by activating KLF7/IL-6/p21 signaling pathway, which is mediated by the GPR84.
Our research may provide a potential target for clinical prevention and treatment of PCa which induced by obesity.
在之前的研究中,我们发现中链脂肪酸辛酸(FFA C8:0)的含量可能是肥胖诱导前列腺癌(PCa)的一个重要危险因素。然而,FFA C8:0 与 PCa 之间的关系尚未报道。在这项研究中,我们通过上调 Krüppel 样因子 7(KLF7)来探讨 FFA C8:0 是否可以促进 PCa 的进展。
我们收集了 PCa 患者和良性前列腺增生(BPH)患者的组织,构建了肥胖型荷瘤小鼠模型,通过高脂肪饮食,观察 PCa 细胞的肿瘤形成能力。体外,通过 CCK8 检测、平板克隆、Transwell 和划痕实验,检测 FFA C8:0 刺激下 PCa 细胞生物学行为的变化。
首先,我们发现患者 PCa 组织中 KLF7 的表达水平较高,KLF7 的表达与促瘤基因 IL-6 呈正相关,而与另一个抑瘤基因 p21 呈负相关。然后,这项研究发现 PCa 细胞在饮食诱导肥胖的小鼠中更容易形成肿瘤。与正常饮食组(ND)相比,高脂肪饮食组(HFD)肿瘤组织中 KLF7 的表达水平更高。此外,我们验证了高浓度的 FFA C8:0 通过激活 KLF7/IL-6/p21 信号通路,促进 PCa 细胞的生物学行为,该通路由 GPR84 介导。
我们的研究可能为肥胖诱导的 PCa 的临床预防和治疗提供一个潜在的靶点。