Andrographolide suppress tumor growth by inhibiting TLR4/NF-κB signaling activation in insulinoma.
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.
1. Vascular Biology Research Institute, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Qian-Qian
QQ
Zhang
1. Vascular Biology Research Institute, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Yi
Y
Ding
1. Vascular Biology Research Institute, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Yan
Y
Lei
1. Vascular Biology Research Institute, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Cui-Ling
CL
Qi
1. Vascular Biology Research Institute, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Xiao-Dong
XD
He
1. Vascular Biology Research Institute, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Tian
T
Lan
1. Vascular Biology Research Institute, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Jiang-Chao
JC
Li
1. Vascular Biology Research Institute, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Ping
P
Gong
3. Department of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College of Jinan University, Guangzhou 510632, China.
Xuesong
X
Yang
2. Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
Jian-Guo
JG
Geng
1. Vascular Biology Research Institute, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Li-Jing
LJ
Wang
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007340:Insulinoma / Q000098:blood supply / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D000970:Antineoplastic Agents; D004224:Diterpenes; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C030419:andrographolide
Andrographolide; growth.; insulinoma