School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu, 210009, PR China.
Department of General Surgery, Rui Jin Hospital, Research Institute of Pancreatic Diseases, School of Medicine, Shanghai JiaoTong University, Shanghai, 200025, PR China.
Carbohydr Polym. 2019 Dec 1;225:115223. doi: 10.1016/j.carbpol.2019.115223. Epub 2019 Aug 20.
A polysaccharide isolated from Strongylocentrotus nudus eggs (SEP) reportedly displays immune activity in vivo. Here, its effect and underlying mechanism in the treatment of pancreatic cancer were investigated. SEP obviously inhibited pancreatic cancer growth by activating NK cells in vitro/vivo via TLR4/MAPKs/NF-κB signaling pathway, The tumor inhibitory rate achieved to 44.5% and 50.8% at a dose of 40 mg/kg in Bxpc-3 and SW1990 nude mice, respectively. Moreover, SEP obviously augmented the Gemcitabine (GEM) antitumor effect by upregulating NKG2D, which improved the sensitivity of NK cells targeting to its ligand MICA; meanwhile, the antitumor inhibitory rate was 68.6% in BxPC-3 tumor-bearing mice. Moreover, SEP reversed GEM-induced apoptosis and atrophy in both spleen and bone marrow via suppressing ROS secretion in vivo. These results suggested that pancreatic cancer was effectively inhibited by SEP-enhanced NK cytotoxicity mediated primarily through TLR4/MAPKs/NF-κB signaling pathway, representing a potential immunotherapy candidate for the treatment of pancreatic cancer.
从海参卵中分离得到的一种多糖（SEP）据称具有体内免疫活性。在这里，研究了其在胰腺癌治疗中的作用和潜在机制。SEP 通过 TLR4/MAPKs/NF-κB 信号通路在体外/体内激活 NK 细胞，明显抑制胰腺癌的生长，在 40mg/kg 剂量下，在 Bxpc-3 和 SW1990 裸鼠中的肿瘤抑制率分别达到 44.5%和 50.8%。此外，SEP 通过上调 NKG2D 明显增强了吉西他滨（GEM）的抗肿瘤作用，提高了 NK 细胞对其配体 MICA 的靶向敏感性；同时，在荷 BxPC-3 肿瘤的小鼠中，抗肿瘤抑制率为 68.6%。此外，SEP 通过抑制体内 ROS 分泌，逆转了 GEM 诱导的脾和骨髓中的细胞凋亡和萎缩。这些结果表明，SEP 通过 TLR4/MAPKs/NF-κB 信号通路增强 NK 细胞的细胞毒性，有效地抑制了胰腺癌，这代表了一种治疗胰腺癌的潜在免疫治疗候选药物。
