Zhang Qian-Qian, Ding Yi, Lei Yan, Qi Cui-Ling, He Xiao-Dong, Lan Tian, Li Jiang-Chao, Gong Ping, Yang Xuesong, Geng Jian-Guo, Wang Li-Jing
1. Vascular Biology Research Institute, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
3. Department of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College of Jinan University, Guangzhou 510632, China.
Int J Biol Sci. 2014 Mar 21;10(4):404-14. doi: 10.7150/ijbs.7723. eCollection 2014.
Insulinomas are rare tumors, and approximately 10% of insulinomas are malignant. Accumulating evidence has implicated that we still lack effective therapy to treat the patients who are diagnosed with rare malignant insulinoma. Previous studies have reported that Andrographolide (Andro) could inhibit cell cycle progression, reduce cell invasion and induce cell apoptosis in many common cancer cells. However, the effects of andro are cell type-dependent. So we emplored the β-TC-6 cells and the RIP1-Tag2 transgenic mouse model of endogenously growing insulinoma model to elucidate the possible anti-cancer effect of Andro on insulinoma, an uncommon type of malignant cancers in this study. Our experiments revealed that Andro significantly inhibited tumor growth at both the early-stage and the advanced-stage of insulinoma through targeting the TLR4/NF-κB signaling pathway. This work initially provides the evidence that the TLR4/NF-κB signaling pathway might be vital as a potential therapeutic target, and also indispensable in Andro-mediated anti-cancer effect in insulinoma.
胰岛素瘤是罕见肿瘤,约10%的胰岛素瘤为恶性。越来越多的证据表明,对于被诊断为罕见恶性胰岛素瘤的患者,我们仍缺乏有效的治疗方法。先前的研究报道,穿心莲内酯(Andro)可抑制许多常见癌细胞的细胞周期进程、减少细胞侵袭并诱导细胞凋亡。然而,穿心莲内酯的作用具有细胞类型依赖性。因此,在本研究中,我们利用β-TC-6细胞和内源性生长的胰岛素瘤模型RIP1-Tag2转基因小鼠模型,来阐明穿心莲内酯对胰岛素瘤这种罕见恶性肿瘤可能的抗癌作用。我们的实验表明,穿心莲内酯通过靶向TLR4/NF-κB信号通路,在胰岛素瘤的早期和晚期均显著抑制肿瘤生长。这项工作初步提供了证据,表明TLR4/NF-κB信号通路作为潜在治疗靶点可能至关重要,并且在穿心莲内酯介导的胰岛素瘤抗癌作用中也不可或缺。