Vincristine sulfate 是一种抗肿瘤长春花生物碱。在细胞周期的 S 期不可逆地与微管 (Ki: 85 nM) 和纺锤体蛋白结合，并干扰有丝分裂纺锤体的形成。

Vincristine binds irreversibly to microtubules (Ki: 85 nM) and spindle proteins in S phase of the cell cycle and interferes with the formation of the mitotic spindle.

Vincristine inhibited tubulin addition (Ki, 0.085 microM). In L-cells, vincristine caused about 25% growth inhibition at 40 nM [1]. Vincristine inhibited SH-SY5Y cell proliferation in a time- and dose-dependent manner (IC50: 0.1 μM). VCR at 0.1 μM induced mitotic arrest and apoptosis, promoted the expression of caspase-3 and -9 and cyclin B while decreasing the expression of cyclin D at 6, 12, 18 and 24 h [2]. Axonal ultrastructural changes induced by vinblastine were studied in vitro at concentrations of 0.05 mM in the cat vagus nerve. Disruption of microtubules, the appearance of paracrystalline structures, and increase in neurofilaments were induced by vinblastine at 0.1 mM [3].

Two multidrug-resistant P388 leukemia sublines, refractory to vincristine when grown as intraperitoneal ascites, were sensitive to necrosis induction when grown as subcutaneous tumours [4]. Following a single bolus injection of vincristine, the chimeras transplanted with wild-type or Mdr1ab KO marrow cells showed no reductions in WBC. In wild-type and KO mice, the absence of P-gp reduced the body clearance of vincristine, but that no further reduction occurred when Mrp1 was also absent [5].

SH-SY5Y cells at a logarithmic phase were seeded in 96-well plates (at 2x10^6/l) and incubated for 12 h until cells formed a monolayer. Wells were randomly chosen for treatment groups and a control group. For the treatment groups, cells were incubated with 200 μl of cell culture medium containing 0.001, 0.01, 0.1, 1 or 10 μM of VCR. In the control group, cells were grown in 200 μl cell culture medium only. Cells were incubated for another 24, 48 and 72 h and then 20 μl of 5 g/l MTT (0.1 mg/l final concentration) was added to each well. After 4 h of incubation, the cell culture supernatant was removed, 150 μl of DMSO was added to each well and the plate was shaken for 10 min. The absorbance of each well was detected at 490 nm (A value) on an ELISA plate reader. The growth inhibition rate of VCR-treated cells was calculated as: Growth inhibition rate % = [(average A value of control group - average A value of VCR-treated group)/average A value of control group] x 100%. This experiment was performed in triplicates [2].

Vincristine (1?mg/ml) was diluted in saline and administered i.v. to wild-type and Mdr1ab/Mrp1 TKO mice, aged 10–14 weeks, at dose levels ranging between 0.125 and 4?mg/kg. Animals were monitored daily and killed when they lost more than 20% of their initial body weight. The MTD was defined as one dose step below the dose where more than one animal in that group had to be killed. Necropsies were performed in wild-type and Mdr1ab/Mrp1 TKO mice receiving vincristine at or near the MTD and killed 2 days later [5].

2068-78-2

C46H58N4O14S

923.04

22-Oxovincaleukoblastine sulfate;硫酸长春新碱;Leurocristine sulfate;Leurocristine

DMSO:93 mg/mL (100.8 mM)
H2O:92.3 mg/mL(100 mM)
Ethanol:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years