Vincristine sulfate is an alkaloidal natural product that binds to microtubule proteins and inhibits the formation of microtubules, thereby inhibiting mitosis in tumor cells. Vincristine sulfate is used as a microtubule destabilizing agent in research studies for the treatment of hematologic neoplasms such as leukemias and lymphomas, as well as in studies related to sarcomas in children.

Microtubule:85 nM (Ki, cell free)

方法: 神经母细胞瘤细胞 SH-SY5Y 用 Vincristine sulfate (0.001-10 µM) 处理 24-72 h，使用 MTT assay 检测细胞活力。
结果: Vincristine 对 SH-SY5Y 细胞增殖的抑制作用具有剂量和时间依赖性。24、48 和 72 h的 IC50 分别为0.113 µM、0.078 µM 和 0.051 µM。[1]
方法: 人白血病细胞 MOLT-4 用 Vincristine sulfate (0.3-3 µM) 和 SAHA (500 nM) 处理 24-48 h，使用 Flow cytometry 检测细胞周期。
结果: 与 SAHA 相比，Vincristine 处理诱导细胞周期的 G2/M 期增加。Vincristine 加 SAHA 的组合在短期治疗后 (24 h) 导致细胞几乎完全停滞在 G2/M 期，随后在长期治疗后 (48 h) 诱导细胞进入 sub-G1 期。[2]

方法: 为检测体内抗肿瘤活性，将 Vincristine sulfate (0.025 mg/kg，静脉注射，每周一次) 和 SAHA (200 mg/kg，口服给药，每天一次) 给药给携带 MOLT-4 异种移植物的 SCID 小鼠，持续 24 天。
结果: 单独用 Vincristine 或 SAHA 治疗的小鼠的 TGD 没有改善。然而，对数秩分析显示，在 MOLT-4 异种移植物模型中，共处理表现出显著的抗肿瘤活性。[2]

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].