State Key Laboratory of Natural Medicines, 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, China.
Carbohydr Polym. 2017 Oct 1;173:360-371. doi: 10.1016/j.carbpol.2017.06.024. Epub 2017 Jun 10.
The polysaccharide SEP has been reported to activate NK and T cells via TLR2/4. Here, the combination of gemcitabine (GEM) and SEP against HepG-2 was investigated. SEP apparently enhanced antitumor activity of gemcitabine against liver cancer through stimulating NKG2D and DAP10/Akt pathway to activate NK cells. The NKG2D upregulation could improve the sensitivity of NK-92 cells targeting to its ligand MICA expressed on HepG-2 cells. Meanwhile, GEM up-regulated MICA expression and attenuated soluble MICA secretion through inhibiting ADAM10 expression, which in turn enhanced the cytotoxicity of NK-92 cells against cancer cells. SEP remarkably enhanced GEM antitumor activity with an inhibitory rate of 79.1% in an H22-bearing mouse model. Moreover, SEP reversed atrophy and apoptosis caused by GEM in both spleen and bone marrow through suppressing ROS secretion in vivo. The data indicated that the combination of SEP and GEM is a potential chemo-immunotherapy strategy for liver cancer treatment clinically.
多糖 SEP 已被报道通过 TLR2/4 激活 NK 和 T 细胞。在这里，研究了吉西他滨 (GEM) 和 SEP 联合用于 HepG-2 的情况。SEP 通过刺激 NKG2D 和 DAP10/Akt 通路激活 NK 细胞，明显增强了吉西他滨对肝癌的抗肿瘤活性。NKG2D 的上调可以提高 NK-92 细胞对 HepG-2 细胞表面表达的其配体 MICA 的靶向敏感性。同时，GEM 通过抑制 ADAM10 的表达而上调 MICA 表达并减弱可溶性 MICA 的分泌，从而增强 NK-92 细胞对癌细胞的细胞毒性。SEP 在 H22 荷瘤小鼠模型中显著增强了 GEM 的抗肿瘤活性，抑制率为 79.1%。此外，SEP 通过抑制体内 ROS 的分泌，逆转了 GEM 在脾和骨髓中引起的萎缩和凋亡。数据表明，SEP 和 GEM 的联合是一种有临床应用潜力的肝癌治疗化疗免疫治疗策略。
