Cucurbitacin I (JSI-124), a natural compound, is a selective inhibitor of JAK2/STAT3 with anti-cancer activity.

Cucurbitacin I的抗癌活性通过降低p-STAT3和MMP-9的表达来实现[1]。将Seax细胞系与Jak/Stat3抑制剂Cucurbitacin I孵育，可以观察到P-Stat3和Stat3的表达随时间和浓度的增加而减少。用30 μM Cucurbitacin I孵育新鲜分离的Sz细胞6小时，能在大部分（73-91%）肿瘤细胞中诱导凋亡[2]。Cucurbitacin I预处理心肌细胞显著抑制由PE引起的细胞增大以及ANF和β-MHC的上调。Cucurbitacin I还抑制了连接组织生长因子（CTGF）和MAPK信号通路、促心肌肥大因子以及TGF-β/Smad信号通路，这些是纤维化的重要促进因素[3]。

Cucurbitacin I与对照组、联合治疗与对照组以及联合治疗与Cucurbitacin I组之间的肿瘤体积差异显著。此外，研究结束时，联合治疗的肿瘤平均重量显著低于对照组。而且，对小鼠体重没有影响[4]。

BALB/c nude (nu/nu) female mice are used. U251 cells (5×10^6 cells in 50 μL of serum-free DMEM) are inoculated subcutaneously into the right flank of 5-week-old female mice after acclimatization for a week. Tumor growth is measured daily with calipers. When the tumors reach a mean volume of 90-120 mm3, animals are randomized into groups. In the first experiment, 16 mice are randomly assigned to Cucurbitacin I (1 mg/kg/day in 20% DMSO in PBS) or drug vehicle control (20% DMSO in PBS) and dosed intraperitoneally with 100 μL of vehicle or drug once daily for 18 days, whereas, in the second, 20 mice are assigned to four groups. Control animals receive 20% DMSO in PBS vehicle, whereas treated animals are injected with Cucurbitacin I (1 mg/kg/day) in 20% DMSO in PBS, CQ (25 mg/kg/day) in 20% DMSO in PBS, and Cucurbitacin I (1 mg/kg/day) plus CQ (25 mg/kg/day) in 20% DMSO in PBS and dosed intraperitoneally with 100 μL of vehicle or drug once daily for 15 days [4].