Lamivudine is an oral nucleoside analogue, which acts as the nucleoside reverse transcriptase inhibitor, with an EC50 of 0.07±0.02μg/ml for anti-hepatitis B virus (HBV) activity[1]. Lamivudine undergoes anabolic phosphorylation by intracellular kinases to form Lamivudine 5′-triphosphate, the active anabolite which prevents HIV-1 and HBV replication by competitively inhibiting viral reverse transcriptase and terminating proviral DNA chain extension [2]. Lamivudine has been used in viral and antitumor studies in various cell and animal models[3].
In vitro, Lamivudine treatment at 300μM in HepG2.2.15 cells for 72 hours significantly reduced the expression of MMP-9, HBsAg, HBeAg, and inhibited the replication of HBV[4]. Treatment of 4μg/ml Lamivudine for 6 days significantly inhibted SDAU1005 virus replication in chick embryo fibroblasts (CEFs) without affecting cell viability[5]. Lamivudine treatment with 500μM for 8 days can stimulate the proliferation of dendritic cells (DC) derived from patients with chronic hepatitis B (CHB), promote the secretion of IL-12 and IL-6, and restore cellular immune function[6].
In vivo, Lamivudine treatment via daily gastric infusion (100mg/kg) in senescence-accelerated mouse prone 8 (SAMP8) mice for 4 weeks significantly improved the ageing status of the mice and alleviated the decline in cognitive ability[7]. Oral administration of 2mg/kg Lamivudine daily for one week reduced the severity of gastric ulcers in a mouse model of ethanol-induced gastric ulcers, and improved the histological features of the gastric mucosa and maintained the integrity of the gastric mucosal barrier[8].
References:
[1] Ying, Clercq D, Neyts. Lamivudine, adefovir and tenofovir exhibit long‐lasting anti‐hepatitis B virus activity in cell culture[J]. Journal of viral hepatitis, 2000, 7(1): 79-83.
[2] Perry C M, Faulds D. Lamivudine: a review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in the management of HIV infection[J]. Drugs, 1997, 53(4): 657-680.
[3] Johnson M A, Moore K H P, Yuen G J, et al. Clinical pharmacokinetics of lamivudine[J]. Clinical pharmacokinetics, 1999, 36(1): 41-66.
[4] Zhang J, Yu H, Sun F Y, et al. Effects of lamivudine on cell proliferation of liver cancer and expressions of HBsAg, HBeAg, and MMP-9 in patients[J]. Eur. Rev. Med. Pharmacol. Sci, 2019, 23: 9093-9098.
[5] Wang Y, Xu S, Li S, et al. Lamivudine inhibits the replication of ALV-J associated acutely transforming virus and its helper virus and tumor growth in vitro and in vivo[J]. Frontiers in Microbiology, 2015, 6: 1306.
[6] Zheng P Y, Zhang D Y, Lu G F, et al. Effects of lamivudine on the function of dendritic cells derived from patients with chronic hepatitis B virus infection[J]. World Journal of Gastroenterology: WJG, 2007, 13(34): 4641.
[7] Li M, Zhao J, Tang Q, et al. Lamivudine improves cognitive decline in SAMP8 mice: Integrating in vivo pharmacological evaluation and network pharmacology[J]. Journal of Cellular and Molecular Medicine, 2021, 25(17): 8490-8503.
[8] Meng X, Liu J, Kang J, et al. Lamivudine protects mice from gastric ulcer by activating PGK1 to suppress ferroptosis[J]. Biochemical Pharmacology, 2024, 227: 116440.
Lamivudine是一种口服核苷类似物，作为核苷类逆转录酶抑制剂，抗乙肝病毒（HBV）活性的EC50值为0.07±0.02μg/ml[1]。Lamivudine通过细胞内激酶发生磷酸化生成活性代谢物拉米夫定三磷酸酯，可竞争性抑制病毒逆转录酶并终止前病毒DNA链延伸，从而阻止HIV-1和HBV复制[2]。Lamivudine已广泛应用于多种细胞和动物模型的病毒及抗肿瘤研究[3]。
在体外，300μM的Lamivudine处理HepG2.2.15细胞72小时可显著降低MMP-9、HBsAg和HBeAg表达，并抑制HBV复制[4]。4μg/ml的Lamivudine处理鸡胚成纤维细胞（CEFs）6天能显著抑制SDAU1005病毒复制且不影响细胞活力[5]。500μM的Lamivudine处理慢性乙肝（CHB）患者来源的树突状细胞（DC）8天可刺激细胞增殖，促进IL-12和IL-6分泌，恢复细胞免疫功能[6]。
在体内，加速衰老SAMP8小鼠经每日胃灌注Lamivudine（100mg/kg，持续4周）后，小鼠的衰老状态显著改善且认知能力下降缓解[7]。乙醇诱导胃溃疡小鼠模型每日口服2mg/kg剂量的Lamivudine（持续1周）可减轻溃疡严重程度，改善胃黏膜组织学特征并维持胃黏膜屏障完整性[8]。