Vinorelbine is an anti-mitotic drug, a semi-synthetic derivative of paclitaxel, that exerts its antitumor effect by inhibiting microtubule polymerization in tumor cells. Vinorelbine is primarily used to treat malignant tumors such as non-small cell lung cancer and metastatic breast cancer[1, 2]. Vinorelbine rapidly and reversibly binds to soluble tubulin, inducing conformational changes, enhancing the affinity of microtubules themselves, significantly reducing the rate of microtubule dynamics (elongation and shortening), and prolonging the duration of microtubules in the attenuated state[3]. Vinorelbine can induce p53 and p21WAFI/CIP1 expression in androgen-dependent (AD) and androgen-independent (AI) prostate cancer cell lines[4]. Vinorelbine can hinder the timely progression of meiosis maturation in mice and induce aneuploidy in mouse oocytes[5].
In vitro, Vinorelbine (0.1-36nM) treatment of HOS and MG-63 osteosarcoma cells for 8-72h inhibited the growth of both cell lines in a dose- and time-dependent manner and induced apoptosis[6]. Vinorelbine (0.5-6nM) treatment of human breast cancer cell lines (MCF 7, ZR 75-1, and T 47-D cells) for 24h inhibited the growth of the three cell lines in a dose-dependent manner and induced apoptosis[7].
In vivo, Vinorelbine (30mg/kg) administered intravenously to mice xenografted with 3LL lung cancer cells almost completely inhibited tumor growth and the production of malignant pleural effusion (MPE), significantly reducing tumor angiogenesis and vascular endothelial growth factor (VEGF) expression[8].
References:
[1] Kumar B, Kumar R, Skvortsova I, et al. Mechanisms of tubulin binding ligands to target cancer cells: updates on their therapeutic potential and clinical trials[J]. Current cancer drug targets, 2017, 17(4): 357-375.
[2] Ngan V K, Bellman K, Hill B T, et al. Mechanism of mitotic block and inhibition of cell proliferation by the semisynthetic Vinca alkaloids vinorelbine and its newer derivative vinflunine[J]. Molecular pharmacology, 2001, 60(1): 225-232.
[3] Capasso A. Vinorelbine in cancer therapy[J]. Current drug targets, 2012, 13(8): 1065-1071.
[4] Liu X M, Jiang J D, Ferrari A C, et al. Unique induction of p21WAF1/CIP1expression by vinorelbine in androgen-independent prostate cancer cells[J]. British journal of cancer, 2003, 89(8): 1566-1573.
[5] Cheng S Y, Yi Z Y, Zhang C H, et al. Vinorelbine administration impedes the timely progression of meiotic maturation and induces aneuploidy in mouse oocytes[J]. Reproductive Toxicology, 2024, 128: 108634.
[6] Roncuzzi L, Marti G, Baiocchi D, et al. Effect of Vinorelbine on cell growth and apoptosis induction in human osteosarcoma in vitro[J]. Oncology reports, 2006, 15(1): 73-77.
[7] Weigel M T, Meinhold-Heerlein I, Bauerschlag D O, et al. Combination of imatinib and vinorelbine enhances cell growth inhibition in breast cancer cells via PDGFR β signalling[J]. Cancer letters, 2009, 273(1): 70-79.
[8] Cui R, Yoshioka M, Takahashi F, et al. Vinorelbine is effective for the malignant pleural effusion associated with lung cancer in mice[J]. Anticancer research, 2008, 28(3A): 1633-1639.
Vinorelbine是一种抗有丝分裂药物，是紫杉醇（Paclitaxel）的一种半合成衍生物，通过抑制肿瘤细胞的微管聚合来发挥抗肿瘤作用，主要用于治疗非小细胞肺癌和转移性乳腺癌等恶性肿瘤[1, 2]。Vinorelbine能够与可溶性微管蛋白的快速且可逆结合，诱导构象变化，增强微管自身的亲和力，显著降低了微管动态的速率（延长和缩短），并延长了微管在衰减状态下的持续时间[3]。Vinorelbine能够在雄激素依赖性（AD）和非依赖性（AI）前列腺癌细胞系中，诱导p53和p21WAFI/CIP1表达[4]。Vinorelbine能够阻碍小鼠减数分裂成熟的及时进展，并诱导小鼠卵母细胞出现非整倍体[5]。
在体外，Vinorelbine（0.1-36nM）处理HOS和MG-63骨肉瘤细胞8-72h，以剂量和时间依赖性方式抑制了两种细胞系的生长，诱导了细胞凋亡[6]。Vinorelbine（0.5-6nM）处理人类乳腺癌细胞系（MCF 7、ZR 75-1和T 47-D细胞）24h，以剂量依赖性方式抑制了三种细胞系的生长，诱导了细胞凋亡[7]。
在体内，Vinorelbine（30mg/kg）通过静脉注射治疗肺癌细胞系3LL细胞异种移植小鼠，几乎完全抑制了小鼠体内肿瘤生长和恶性胸腔积液（MPE）的产生，显著降低了肿瘤的新血管生成和血管内皮生长因子（VEGF）的表达[8]。