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.