Dihydroartemisinin inhibits colon cancer cell viability by inducing apoptosis through up-regulation of PPARγ expression.
Dihydroartemisinin inhibits colon cancer cell viability by inducing apoptosis through up-regulation of PPARγ expression.
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DOI：
10.1016/j.sjbs.2017.02.002
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发表时间：
2018-03
影响因子：
4.4
通讯作者：
Pan ZZ
中科院分区：
文献类型：
--
作者：
Lu ZH;Peng JH;Zhang RX;Wang F;Sun HP;Fang YJ;Wan DS;Pan ZZ
本研究旨在探讨双氢青蒿素对结肠癌细胞增殖和凋亡的影响。四甲基偶氮唑盐比色法结果显示，双氢青蒿素对SW 948细胞活力的抑制作用与浓度和时间呈剂量和时间依赖关系。30和50µM双氢青蒿素作用48h后，细胞存活率分别降至45%和24%，细胞形态观察显示，双氢青蒿素作用后，细胞形态变圆，形成簇状。Western印迹分析显示，双氢青蒿素可显著增强caspase-3的活性和裂解PARP的表达。双氢青蒿素可显著提高SW948细胞PPARγ的活性。与对照组相比，50µM双氢青蒿素可显著降低SW948细胞的迁移能力(P<0.005)，并抑制基质金属蛋白酶-2和-9的表达水平。双氢青蒿素治疗组小鼠30天后给予20 mg/kg剂量的双氢青蒿素可明显抑制结肠癌的形成。因此，双氢青蒿素通过诱导细胞凋亡和增加PPARγ的表达来抑制结肠癌的生长。因此，双氢青蒿素可用于结肠癌的治疗。
The present study was aimed to investigate the effect of dihydroartemisinin on the colon cancer cell proliferation and apoptosis. The results from MTT assay revealed a concentration and time dependent relation between the inhibition of SW 948 cell viability and dihydroartemisinin addition. The viability of SW 948 cells was reduced to 45 and 24% on treatment with 30 and 50 µM, respectively concentrations of dihydroartemisinin after 48 h. Morphological examination of SW 948 cells showed attainment of rounded shape and cluster formation on treatment with dihydroartemisinin. Western blot analysis showed a significant increase in the activation of caspase-3 and expression of cleaved PARP by dihydroartemisinin treatment. The activation of PPARγ was increased significantly in SW 948 cells by treatment with dihydroartemisinin. Compared to control, the migration potential of SW 948 cells was reduced significantly (p < 0.005) and the expression levels of MMP-2 and -9 inhibited by dihydroartemisinin at 50 µM concentration. In the dihydroartemisinin treatment group colon tumor formation was significantly inhibited on treatment with 20 mg/kg doses of dihydroartemisinin after 30 days. Therefore, dihydroartemisinin inhibits colon cancer growth by inducing apoptosis and increasing the expression of PPARγ. Thus dihydroartemisinin can be used for the treatment of colon cancer.
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