Tasquinimod is an orally active inhibitor of histone deacetylase 4 (HDAC4) and S100 calcium-binding protein A9 (S100A9)[1]. Tasquinimod inhibits angiogenesis and reduces immunosuppression within tumors, and is commonly used in the research and treatment of metastatic castration-resistant prostate cancer (mCRPC)[2,3,4].
In vitro, treatment of SKOV3/DDP cells with Tasquinimod (40μM) for 12-48h resulted in significantly downregulated Bcl-2 expression and significantly upregulated cleaved-Caspase-3 expression compared to controls. Overexpression of HDAC4 partially reversed the pro-apoptotic effect of Tasquinimod[5]. Treatment of SKOV3 cells with Tasquinimod (40μM) for 48h reduced the relative scratch width and inhibited cell migration ability[6].
In vivo, oral administration of Tasquinimod (10mg/kg/day) for 9 weeks in mice with intratibial injections of LNCaP-19 cells reduced the tumor incidence in bone from 7/10 in the control group to 2/10 in the treatment group[7]. Oral administration of Tasquinimod (10mg/kg/day) for 3 weeks in LNCaP tumor-bearing mice significantly increased TSP1 protein levels in tumor tissues, and the ratio of intact TSP1 (approximately 150-160kDa) to β-actin was markedly increased in the treatment group[8].
References:
[1] Fan R, Satilmis H, Vandewalle N, et al. Tasquinimod suppresses tumor cell growth and bone resorption by targeting immunosuppressive myeloid cells and inhibiting c-MYC expression in multiple myeloma[J]. Journal for Immunotherapy of Cancer, 2023, 11(1): e005319.
[2] Raymond E, Dalgleish A, Damber J E, et al. Mechanisms of action of tasquinimod on the tumour microenvironment[J]. Cancer Chemotherapy and Pharmacology, 2014, 73(1): 1-8.
[3] Gupta N, Al Ustwani O, Shen L, et al. Mechanism of action and clinical activity of tasquinimod in castrate-resistant prostate cancer[J]. OncoTargets and Therapy, 2014: 223-234.
[4] Mehta A R, Armstrong A J. Tasquinimod in the treatment of castrate-resistant prostate cancer–current status and future prospects[J]. Therapeutic Advances in Urology, 2016, 8(1): 9-18.
[5] Li Z, Wu Y H, Guo Y Q, et al. Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway[J]. The Korean Journal of Physiology & Pharmacology, 2025, 29(2): 191-204.
[6] Lin Y, Liu Y Q, Zhu K A, et al. Tasquinimod enhances the sensitivity of ovarian cancer cells to cisplatin by regulating the Nur77-Bcl-2 apoptotic pathway[J]. Advances in Clinical and Experimental Medicine, 2024, 33(2): 151-161.
[7] Jennbacken K, Welén K, Olsson A, et al. Inhibition of metastasis in a castration resistant prostate cancer model by the quinoline-3-carboxamide tasquinimod (ABR-215050)[J]. The Prostate, 2012, 72(8): 913-924.
[8] Olsson A, Björk A, Vallon-Christersson J, et al. Tasquinimod (ABR-215050), a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors[J]. Molecular Cancer, 2010, 9(1): 107.
Tasquinimod是一种具有口服活性的组蛋白去乙酰化酶4（HDAC4）和S100 钙结合蛋白A9（S100A9）抑制剂[1]。Tasquinimod可抑制血管生成，并减少肿瘤内的免疫抑制作用，通常用于转移性去势抵抗性前列腺癌（mCRPC）的研究和治疗[2,3,4]。
在体外，Tasquinimod（40μM）处理SKOV3/DDP细胞12-48h，较对照Bcl-2表达显著下调，cleaved-Caspase-3表达显著上调，过表达HDAC4可部分逆转Tasquinimod的促凋亡效应[5]。Tasquinimod（40μM）处理SKOV3细胞48h，相对划痕宽度减小，细胞迁移能力被抑制[6]。
在体内，Tasquinimod（10mg/kg/day）通过口服治疗胫骨内注射LNCaP-19细胞的小鼠9周，肿瘤在骨内的出现率从对照组的7/10只降至治疗组的2/10只[7]。Tasquinimod（10mg/kg/day）通过口服治疗LNCaP荷瘤小鼠3周，肿瘤组织中的TSP1蛋白水平显著升高，完整TSP1（约150-160kD）与β-actin的比值在治疗组中明显增加[8]。