Cyclic di-GMP is a stimulator of interferon genes (STING) agonist[1]. Cyclic di-GMP is a cyclic dinucleotide and a bacterial second messenger that regulates biofilm formation, motility and virulence of different bacteria[2]. Cyclic di-GMP has anti-cancer cell proliferation activity and can also induce increased CD4 receptor expression and cell cycle arrest[3].
In vitro, treatment of human cecal adenocarcinoma H508 cells with Cyclic di-GMP (0.5-50μM) for 5 days inhibited basal cell proliferation as well as cell proliferation stimulated by acetylcholine and epidermal growth factor (EGF)[4]. Treatment of lymphoblastoid CD4+ Jurkat cell line with Cyclic di-GMP (50μM) significantly increased intracellular CD4 expression and led to S phase arrest of the cell cycle[5].
In vivo, Cyclic di-GMP (100µg) was administered intravenously to mice bearing B16F10 cell xenografts, which effectively enhanced the immune response produced by the TriVax vaccine and induced the production of more antigen-specific CD8 T cells in mice[6].
References:
[1] Burdette D L, Monroe K M, Sotelo-Troha K, et al. STING is a direct innate immune sensor of cyclic di-GMP[J]. Nature, 2011, 478(7370): 515-518.
[2] Jenal U, Reinders A, Lori C. Cyclic di-GMP: second messenger extraordinaire[J]. Nature Reviews Microbiology, 2017, 15(5): 271-284.
[3] Li A, Yi M, Qin S, et al. Activating cGAS-STING pathway for the optimal effect of cancer immunotherapy[J]. Journal of hematology & oncology, 2019, 12: 1-12.
[4] Karaolis D K R, Cheng K, Lipsky M, et al. 3′, 5′-Cyclic diguanylic acid (c-di-GMP) inhibits basal and growth factor-stimulated human colon cancer cell proliferation[J]. Biochemical and biophysical research communications, 2005, 329(1): 40-45.
[5] Steinberger O, Lapidot Z, Ben-Ishai Z, et al. Elevated expression of the CD4 receptor and cell cycle arrest are induced in Jurkat cells by treatment with the novel cyclic dinucleotide 3′, 5′-cyclic diguanylic acid[J]. FEBS letters, 1999, 444(1): 125-129.
[6] Wang Z, Celis E. STING activator c-di-GMP enhances the anti-tumor effects of peptide vaccines in melanoma-bearing mice[J]. Cancer Immunology, Immunotherapy, 2015, 64: 1057-1066.
Cyclic di-GMP是一种干扰素基因刺激因子（STING）激动剂[1]。Cyclic di-GMP是一种环状二核苷酸，是细菌第二信使，能够调节不同细菌的生物膜形成、运动性和毒力[2]。Cyclic di-GMP具有抗癌细胞增殖活性，还能够诱导CD4受体表达升高和细胞周期停滞[3]。
在体外，Cyclic di-GMP（0.5-50μM）处理人类盲肠腺癌H508细胞5天，抑制了细胞基础增殖以及乙酰胆碱和表皮生长因子（EGF）刺激的细胞增殖[4]。Cyclic di-GMP（50μM）处理淋巴母细胞CD4+ Jurkat细胞系，显著提高了细胞内CD4的表达，导致了细胞周期S期阻滞[5]。
在体内，Cyclic di-GMP（100µg）通过静脉注射治疗B16F10细胞异种移植小鼠，有效增强了TriVax疫苗产生的免疫反应强度，诱导了小鼠体内产生更多抗原特异性CD8 T细胞[6]。