Pentamidine is a broad-spectrum anti-infective agent that interferes with polyamine synthesis and RNA polymerase activity, demonstrating efficacy against a variety of parasites, protozoa, and fungi[1,2]. As a well-established diamidine drug with a long history of clinical use, Pentamidine is widely employed for the treatment of Pneumocystis pneumonia, leishmaniasis, and trypanosomiasis, and is also commonly used in research related to infectious diseases[3].
In vitro, treatment of various human malignant cell lines (WM9, DU145, C4-2, Hey, WM480, and A549) with Pentamidine (0-10μM) for 6 days resulted in concentration-dependent inhibition of cell growth across all six lines, with complete suppression observed at 10μM[4]. In LPS-induced (20ng/mL) RAW264.7 cells, 24h treatment with Pentamidine (1, 10, 100μM) concentration-dependently suppressed the overexpression of pro-inflammatory cytokines TNF-α and IL-1β at both mRNA and protein levels[5]. Exposure of HeLa cells to γ-irradiation (5Gy) in the presence of Pentamidine (0.05mM) disrupted mitotic progression and led to an increase in multinucleated cells[6].
In vivo, intramuscular administration of Pentamidine (6-10mg/kg (0.25mg/mouse); every 2 days) in 6-week-old nude mice inoculated with WM9 cells significantly inhibited tumor growth throughout the 16-week study period. No significant abnormalities were observed, and the mice exhibited steady weight gain[4]. In a LPS-induced (25mg/kg; i.p.) septic C57BL/6 mouse model, intraperitoneal injection of Pentamidine (10mg/kg; once a day) for 4 days prolonged survival, attenuated systemic inflammation, and ameliorated LPS-induced damage in the liver, kidney, and lungs[5]. Treatment with Pentamidine (0.8, 4mg/kg) in dextran sodium sulphate (DSS)-induced acute colitis CD-1 mice resulted in comprehensive improvement of colitis-related intestinal symptoms, preserved colon length, and prevented splenomegaly[7].
References:
[1] HAFIZ S, KYRIAKOPOULOS C. Pentamidine[M]//StatPearls. Treasure Island (FL): StatPearls Publishing, 2025.
[2] SANDS M, KRON M A, BROWN R B. Pentamidine: a review[J]. Reviews of infectious diseases, 1985, 7(5): 625-6344.
[3] BRAY P G, BARRETT M P, WARD S A, et al. Pentamidine uptake and resistance in pathogenic protozoa: past, present and future[J]. Trends in parasitology, 2003, 19(5): 232-239.
[4] PATHAK M K, DHAWAN D, LINDNER D J, et al. Pentamidine is an inhibitor of PRL phosphatases with anticancer activity[J]. Molecular cancer therapeutics, 2002, 1(14): 1255-1264.
[5] WU S, LIN C, ZHANG T, et al. Pentamidine alleviates inflammation and lipopolysaccharide-induced sepsis by inhibiting TLR4 activation via targeting MD2[J]. Frontiers in pharmacology, 2022, 13: 835081.
[6] KOBAYASHI J, KATO A, OTA Y, et al. Bisbenzamidine derivative, pentamidine represses DNA damage response through inhibition of histone H2A acetylation[J]. Molecular cancer, 2010, 9(1): 34.
[7] ESPOSITO G, CAPOCCIA E, SARNELLI G, et al. The antiprotozoal drug pentamidine ameliorates experimentally induced acute colitis in mice[J]. Journal of neuroinflammation, 2012, 9(1): 277.
Pentamidine是一种可干扰多胺合成和RNA聚合酶活性的广谱抗感染剂，对多种寄生虫、原生动物和真菌都具有活性[1,2]。Pentamidine作为一种使用历史悠久的二脒类药物，已被广泛应用于肺孢子虫肺炎、利什曼病和锥虫病等的治疗，也常被用于相关感染性疾病的研究[3]。
在体外，Pentamidine（0-10μM）处理不同的人类恶性肿瘤WM9、DU145、C4-2、Hey、WM480和A549细胞6天，所有六种细胞系的生长均被Pentamidine以浓度依赖性的方式抑制，并在10μM时细胞的生长完全受到抑制[4]。Pentamidine（1, 10, 100μM）处理脂多糖LPS诱导（20ng/mL）的RAW264.7细胞24h，浓度依赖性地抑制了LPS诱导的促炎细胞因子TNF-α和1L-1β在mRNA和蛋白水平的过度产生[5]。用含有Pentamidine（0.05mM）的γ-射线（5Gy）照射HeLa细胞，会影响有丝分裂的进行并导致多核细胞数量的增加[6]。
在体内，Pentamidine（6~10mg/kg (0.25mg/mouse); every 2 days）通过臀部肌肉注射治疗接种了WM9细胞的6周龄裸鼠，在16周的研究期间，可显著抑制WM9细胞的生长，且小鼠未出现明显异常，体重还稳步增长[4]。Pentamidine（10mg/kg; once a day）通过腹腔注射治疗由LPS诱导（25mg/kg; i.p.）的脓毒症C57BL/6小鼠4天，延长了小鼠的存活时间，并减轻了LPS引起的小鼠肝脏、肾脏和肺脏损害及全身炎症[5]。Pentamidine（0.8, 4mg/kg）处理dextran sodium sulphate (DSS)诱导的急性结肠炎CD-1小鼠，小鼠与结肠炎相关的肠道症状得到全面改善，并能保持结肠长度并防止小鼠的脾肿大[7]。