Chen Shiyou, Liang Lunan, Wang Ying, Diao Jianhun, Zhao Chunxiong, Chen Gang, He Yunfeng, Luo Chunli, Wu Xiaohou, Zhang Yao
Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
Department of Reproductive Medicine, The Affiliated Hospital of Jining Medical College, Jining, Shandong 272000, P.R. China.
Mol Med Rep. 2015 Nov;12(5):6727-37. doi: 10.3892/mmr.2015.4230. Epub 2015 Aug 20.
Novel therapeutic strategies to improve clinical efficacy in patients with renal cell carcinoma (RCC) are required. The possibility of combination therapy with Lycium barbarum polysaccharides (LBP) and recombinant interferon (IFN)‑α2b remains to be elucidated in RCC. The present study investigated the putative synergistic immunotherapeutic roles of LBP and IFN‑α2b against RCC in vitro and in vivo. The mouse RCC cell line, Renca, was used for in vitro experiments. Treatment of the cells with a combination of LBP and IFN‑α2b markedly inhibited cell proliferation, retarded cell cycle growth and promoted apoptosis in the Renca cells. Western blot analysis revealed that LBP and IFN‑α2b synergistically downregulated the expression levels of cyclin D1, c‑Myc and Bcl‑2, and upregulated the expression of the antiapoptotic protein, Bax. Myeloid‑derived suppressor cells (MDSCs) were markedly upregulated during tumour progression and promoted tumour growth by inhibiting the T‑cell‑mediated immune response. In vivo, a marked reduction in the MDSC ratio and tumour volume was observed in a group receiving combined treatment with LBP and IFN‑α2b in a xenograft tumour model. In conclusion, the present study suggested that the combination of LBP and IFN‑α2b is likely to be more effective in treating murine RCC compared with the less pronounced immunotherapeutic effects of administering LBP or IFN-α2b alone.
需要新的治疗策略来提高肾细胞癌(RCC)患者的临床疗效。枸杞多糖(LBP)与重组干扰素(IFN)-α2b联合治疗在RCC中的可能性仍有待阐明。本研究在体外和体内研究了LBP和IFN-α2b对RCC的假定协同免疫治疗作用。小鼠RCC细胞系Renca用于体外实验。LBP和IFN-α2b联合处理细胞显著抑制Renca细胞的增殖,阻滞细胞周期进展并促进其凋亡。蛋白质免疫印迹分析显示,LBP和IFN-α2b协同下调细胞周期蛋白D1、c-Myc和Bcl-2的表达水平,并上调抗凋亡蛋白Bax的表达。髓源性抑制细胞(MDSC)在肿瘤进展过程中显著上调,并通过抑制T细胞介导的免疫反应促进肿瘤生长。在体内,在异种移植肿瘤模型中,接受LBP和IFN-α2b联合治疗的组中观察到MDSC比例和肿瘤体积显著降低。总之,本研究表明,与单独给予LBP或IFN-α2b时不太明显的免疫治疗效果相比,LBP和IFN-α2b联合使用可能对治疗小鼠RCC更有效。