Thymalfasin (Thymosin α1) is a short, highly charged, and inherently disordered protein with immunoregulatory effects[1]. Thymalfasin can increase the expression of major histocompatibility complex (MHC) antigens and β2 microglobulin on the cell surface, thereby increasing the expression of virus-specific antigens and inhibiting virus replication[2]. Thymalfasin has been widely used to inhibit tumor progression and alleviate inflammatory responses in cellular and animal models[3].
In vitro, Thymalfasin treatment for 24 hours inhibited SNK6 cell proliferation with an IC50 value of 1.334μmol/ml[4]. Treatment of HepG2 cells with 50μg/ml Thymalfasin for 12 hours induced cell cycle arrest and inhibited Akt phosphorylation at Ser473[5]. Treatment with 130μM Thymalfasin for 48h induced apoptosis and DNA damage in ZR-75-1 cells and MCF-7 cells[6].
In vivo, Thymalfasin, administered intraperitoneally at a dose of 0.6mg/kg/day for 5 consecutive days, improved survival and reduced tumor burden in MC38 cell-xenograft mouse models receiving hyperthermic intraperitoneal chemotherapy (HIPEC)[7]. In a mouse model of C. albicans infection, intraperitoneal injection of 200μg/kg/day Thymalfasin for 7 consecutive days alleviated C. albican-induced gastrointestinal inflammation, increased IL-22 levels, and reduced fungal growth in the liver[8].
References:
[1] Hoch K, Volk D E. Structures of thymosin proteins[J]. Vitamins and Hormones, 2016, 102: 1-24.
[2] Tao N, Xu X, Ying Y, et al. Thymosin α1 and its role in viral infectious diseases: the mechanism and clinical application[J]. Molecules, 2023, 28(8): 3539.
[3] Dominari A, Hathaway III D, Pandav K, et al. Thymosin alpha 1: a comprehensive review of the literature[J]. World journal of virology, 2020, 9(5): 67.
[4] Chen M, Jiang Y, Cai X, et al. Combination of Gemcitabine and Thymosin alpha 1 exhibit a better anti-tumor effect on nasal natural killer/T-cell lymphoma[J]. International Immunopharmacology, 2021, 98: 107829.
[5] Qin Y, Chen F D, Zhou L, et al. Proliferative and anti-proliferative effects of thymosin α1 on cells are associated with manipulation of cellular ROS levels[J]. Chemico-biological interactions, 2009, 180(3): 383-388.
[6] Guo Y, Chang H, Li J, et al. Thymosin alpha 1 suppresses proliferation and induces apoptosis in breast cancer cells through PTEN-mediated inhibition of PI3K/Akt/mTOR signaling pathway[J]. Apoptosis, 2015, 20(8): 1109-1121.
[7] Nevo N, Goldstein A L, Bar-David S, et al. Thymosin alpha 1 as an adjuvant to hyperthermic intraperitoneal chemotherapy in an experimental model of peritoneal metastases from colonic carcinoma[J]. International Immunopharmacology, 2022, 111: 109166.
[8] Bellet M M, Borghi M, Pariano M, et al. Thymosin alpha 1 exerts beneficial extrapulmonary effects in cystic fibrosis[J]. European Journal of Medicinal Chemistry, 2021, 209: 112921.
Thymalfasin (Thymosin α1)是一种短链、高电荷且天然无序的免疫调节蛋白[1]。Thymalfasin能增强细胞表面主要组织相容性复合体(MHC)抗原和β2微球蛋白的表达，从而提升病毒特异性抗原呈递效率并抑制病毒复制[2]。Thymalfasin已广泛应用于细胞和动物模型中抑制肿瘤进展及缓解炎症反应[3]。
在体外，Thymalfasin处理24小时可抑制SNK6细胞增殖，IC50值为1.334μmol/ml[4]。使用50μg/ml的Thymalfasin处理HepG2细胞12小时，能诱导细胞周期阻滞并抑制Akt蛋白Ser473位点的磷酸化[5]。以130μM的Thymalfasin处理ZR-75-1和MCF-7细胞48小时，可诱导细胞凋亡与DNA损伤[4]。
在体内，连续5日每日腹腔注射0.6mg/kg/day剂量的Thymalfasin，能提高接受腹腔热灌注化疗(HIPEC)的MC38移植瘤小鼠模型的生存率并减轻肿瘤负荷[7]。在白念珠菌感染小鼠模型中，连续7日每日腹腔注射200μg/kg/day剂量的Thymalfasin，可缓解白念珠菌诱导的胃肠道炎症，提升IL-22水平并减少肝脏中的真菌定植[8]。