Taxol inhibits neointimal smooth muscle cell accumulation after angioplasty in the rat.

Abstract

Despite significant improvements in the primary success rate of the medical and surgical treatments for atherosclerotic disease, including angioplasty, bypass grafting, and endarterectomy, secondary failure due to late restenosis continues to occur in 30-50% of individuals. Restenosis and the later stages in atherosclerotic lesions are due to a complex series of fibroproliferative responses to vascular injury involving potent growth-regulatory molecules (such as platelet-derived growth factor and basic fibroblast growth factor) and resulting in vascular smooth muscle cell (VSMC) proliferation, migration, and neointimal accumulation. We show here, based on experiments with both taxol and deuterium oxide, that microtubules are necessary for VSMCs to undergo the multiple transformations contributing to the development of the neointimal fibroproliferative lesion. Taxol was found to interfere both with platelet-derived growth factor-stimulated VSMC migration and with VSMC migration and with VSMC proliferation, at nanomolar levels in vitro. In vivo, taxol prevented medial VSMC proliferation and the neointimal VSMC accumulation in the rat carotid artery after balloon dilatation and endothelial denudation injury. This effect occurred at plasma levels approximately two orders of magnitude lower than that used clinically to treat human malignancy (peak levels achieved in this model were -50-60 nM). Taxol may therefore be of therapeutic value in preventing human restenosis with minimal toxicity. (J. Clin. Invest. 1995Invest. . 95:1869Invest. -1876

Paclitaxel Interrupts TGF-β1 Signaling Between Gallbladder Epithelial Cells and Myofibroblasts

“…Certainly, PT has a myriad of cellular effects that can be considered "toxic", but our results point to more subtle and nuanced effects on cellular functions. In this respect, our results are in accord with the effects of low dose PT on other cell types such as macrophages and vascular smooth muscle cells [14,15,34].…”

“…The lipophilic PT molecule is rapidly taken up by cells [32], and has a long duration of action, even after a single dose applied topically [29,33]. Its effectiveness after local treatment has been demonstrated by inhibition of proliferation and migration of vascular smooth muscle cell in vitro and in vivo [31,34], and suppression of epithelial proliferation in a rat model of PC [12]. The inhibitory effects of PT on fibrogenesis in the biliary system raise the prospect that stents eluting this compound might be an effective means to prevent recurrent biliary strictures, a concept that has recently been demonstrated in a porcine model [35].…”

Proliferation, migration and invasion of human glioma cells exposed to paclitaxel (Taxol) in vitro

“…Thus, the present study confirms other studies (Stracke et al, 1993;Verschueren et al, 1994;Sollott et al, 1995), but contradicts the findings of Silbergeld et al (1995) who found that paclitaxel increased the motility of glioma cells.…”

In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid–polymeric nanoparticles

“…Given the limited availability of prior data, it is difficult to compare therapeutic systemic doses of paclitaxel in rats for preventing arterial stenosis. However, the doses used in this efficacy study (0.3 mg/kg and 1 mg/kg) appear to be comparable to, or lower than, previous studies (19,39).…”