Department of Urology, Second Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
Department of Oncology, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
Steroids. 2019 Oct;150:108445. doi: 10.1016/j.steroids.2019.108445. Epub 2019 Jul 8.
Low vitamin D status has been associated with increased risks of renal cell carcinoma (RCC). This study aimed to analyze the link between low vitamin D status and interleukin (IL)-6/STAT3 hyper-activation in clear cell RCC (ccRCC) patients. Forty-three newly diagnosed ccRCC patients and 86 age- and sex-matched controls were recruited. The association between low vitamin D status and IL-6/STAT3 hyper-activation was analyzed. Proliferation makersand STAT3 signal were evaluated. As expected, serum IL-6 level was higher in ccRCC patients than in controls. Moreover, serum IL-6 level was reversely correlated with serum 25(OH)D in ccRCC patients but not in controls. In addition, STAT3 signaling was hyper-activated in cancerous tissue. CcRCC patients were divided into three groups according to serum 25(OH)D level: vitamin D sufficiency (VitD-S, ≥30 ng/ml), vitamin D insufficiency (VitD-I, ≥20 and <30 ng/ml) or vitamin D deficiency (VitD-D, <20 ng/ml). Serum IL-6 was higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. Cancerous pSTAT3 level was higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The number of pSTAT3 nuclei in cancerous tissue was more in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The expressions of cancerous PCNA, cyclin D1 and Ki-67, three markers of proliferation, were higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The in vitro experiments showed that active vitamin D3 inhibited LPS-induced STAT3 phosphorylation in ACHN cells. Our results provide evidence that low vitamin D status is correlated with hyper-activation of cancerous IL-6/STAT3 and proliferation in ccRCC patients.
维生素 D 水平低下与肾细胞癌 (RCC) 风险增加有关。本研究旨在分析低维生素 D 状态与透明细胞 RCC (ccRCC) 患者中白细胞介素 (IL)-6/STAT3 过度激活之间的联系。招募了 43 名新诊断的 ccRCC 患者和 86 名年龄和性别匹配的对照者。分析了低维生素 D 状态与 IL-6/STAT3 过度激活之间的关系。评估了增殖标志物和 STAT3 信号。正如预期的那样，ccRCC 患者的血清 IL-6 水平高于对照组。此外，ccRCC 患者的血清 IL-6 水平与血清 25(OH)D 呈负相关，但对照组则不然。此外，STAT3 信号在癌组织中过度激活。根据血清 25(OH)D 水平，将 ccRCC 患者分为三组：维生素 D 充足 (VitD-S，≥30ng/ml)、维生素 D 不足 (VitD-I，≥20 和 <30ng/ml) 或维生素 D 缺乏 (VitD-D，<20ng/ml)。VitD-D 的 ccRCC 患者的血清 IL-6 高于 VitD-S/VitD-I 的患者。VitD-D 的 ccRCC 患者的癌组织 pSTAT3 水平高于 VitD-S/VitD-I 的患者。VitD-D 的 ccRCC 患者癌组织中 pSTAT3 核的数量多于 VitD-S/VitD-I 的患者。VitD-D 的 ccRCC 患者的癌组织中增殖标志物 PCNA、cyclin D1 和 Ki-67 的表达高于 VitD-S/VitD-I 的患者。体外实验表明，活性维生素 D3 抑制了 LPS 诱导的 ACHN 细胞中 STAT3 的磷酸化。我们的研究结果提供了证据，表明低维生素 D 状态与 ccRCC 患者中癌性 IL-6/STAT3 的过度激活和增殖有关。
