School of Chemical Engineering, Harbin Institute of Technology, 73 Huanghe Road, Nangang District, Harbin 150090, P. R. China.
School of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao 066004, P. R. China.
Food Funct. 2017 Jan 25;8(1):151-166. doi: 10.1039/c6fo01235c.
The previous study evaluated the antitumor activity and the underlying mechanism of the purified polyphenols from pinecones of Pinus koraiensis (PPP-40) using a tumor-bearing S180 mice model. This study was designed to evaluate the protective effects of PPP-40 on spleen tissues of S180 mice in vivo. Pretreatment with PPP-40 (150 mg per kg BW per D) could significantly inhibit tumor growth, enhance spleen index and prevent the decline of haematological parameters of S180 mice induced by the tumor microenvironment. Moreover, the treatment with PPP-40 was shown to significantly inhibit splenocyte apoptosis by TUNEL staining and flow cytometry, characterized by the inhibition of splenocyte cycle (G0/G1) arrest, increase in the percentages of splenic T lymphocytes (CD3+ T cells) and T cell subsets (CD3+CD4+ and CD3+CD8+ T cells), as well as the production of T cell-related cytokines (IL-2, IL-12, and TNF-α) in splenocytes exposed to the tumor microenvironment. These effects were associated with a decrease in oxidative stress, as evidenced by the changes in the SOD, GSH-Px, GSH and MDA levels of liver and spleen tissues of S180 mice. Furthermore, the protective effect of PPP-40 on spleen tissues was deeply analyzed by detecting apoptosis-related proteins using immunohistochemistry staining. The results indicated that the protective multi-mechanisms of action also were associated with the inhibition of apoptosis through down-regulation protein expressions of Bax, caspase-9, caspase-8 caspase-3, Fas and up-regulation of the expressions of Bcl-2. These results suggested that PPP-40 is a natural antitumor agent and possesses strong immunomodulatory activities by protecting the spleen tissues of tumor-bearing S180 mice.
先前的研究采用荷瘤 S180 小鼠模型评价了红松松果中纯化多酚（PPP-40）的抗肿瘤活性及其作用机制。本研究旨在评估 PPP-40 对 S180 荷瘤小鼠脾脏组织的保护作用。PPP-40（150mg/kgBW/d）预处理可显著抑制肿瘤生长，提高脾脏指数，并防止肿瘤微环境引起的 S180 小鼠血液学参数下降。此外，PPP-40 处理可通过 TUNEL 染色和流式细胞术显著抑制脾细胞凋亡，表现为抑制脾细胞周期（G0/G1）阻滞，增加脾 T 淋巴细胞（CD3+T 细胞）和 T 细胞亚群（CD3+CD4+和 CD3+CD8+T 细胞）的比例，以及增加肿瘤微环境中脾细胞产生 T 细胞相关细胞因子（IL-2、IL-12 和 TNF-α）。这些作用与氧化应激的降低有关，这可以从 S180 荷瘤小鼠肝脾组织中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、谷胱甘肽（GSH）和丙二醛（MDA）水平的变化中得到证明。此外，通过免疫组织化学染色检测凋亡相关蛋白，深入分析了 PPP-40 对脾脏组织的保护作用。结果表明，PPP-40 的保护作用机制还与其通过下调 Bax、caspase-9、caspase-8、caspase-3、Fas 的蛋白表达，上调 Bcl-2 的表达来抑制细胞凋亡有关。这些结果表明，PPP-40 是一种天然抗肿瘤药物，通过保护荷瘤 S180 小鼠的脾脏组织，具有很强的免疫调节活性。
