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400021 重庆,重庆市中医院药剂科
[梅基雄,E-mail: mjx0025@163.comMEI Jixiong, E-mail: mjx0025@163.com
收稿:2017-10-15,
修回:2017-12-05,
纸质出版:2018-03-15
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刘洪伟, 梅基雄. 双氢青蒿素通过Wnt/β-catenin信号通路抑制胃癌细胞的增殖和侵袭[J]. 第三军医大学学报, 2018,40(5):387-394.
Hongwei LIU, Jixiong MEI. Dihydroartemisinin inhibits proliferation and invasion in human gastric cancer cells through suppression of Wnt/β-catenin signaling pathways[J]. Journal of Third Military Medical University, 2018, 40(5): 387-394.
刘洪伟, 梅基雄. 双氢青蒿素通过Wnt/β-catenin信号通路抑制胃癌细胞的增殖和侵袭[J]. 第三军医大学学报, 2018,40(5):387-394. DOI: 10.16016/j.1000-5404.201710089.
Hongwei LIU, Jixiong MEI. Dihydroartemisinin inhibits proliferation and invasion in human gastric cancer cells through suppression of Wnt/β-catenin signaling pathways[J]. Journal of Third Military Medical University, 2018, 40(5): 387-394. DOI: 10.16016/j.1000-5404.201710089.
目的
2
探讨双氢青蒿素(dihydroartemisinin
DHA)对胃癌细胞增殖、侵袭和迁移能力的影响及其可能的分子机制。
方法
2
用不同浓度(10、20、40 μmol/L)的DHA分别作用于人胃癌BGC-823和SGC-7901细胞,采用MTT法、划痕实验、Transwell法和流式细胞术分别检测细胞的增殖能力、迁移能力、侵袭能力和细胞周期与凋亡情况。Western blot检测细胞中DVL2、GSK-3β、p-GSK-3β、β-catenin和Cyclin D1等蛋白的表达量。
结果
2
不同浓度的DHA可以抑制胃癌细胞的增殖、迁移和侵袭,且呈浓度依赖性增长(
P
<
0.05)。DHA作用48 h后,细胞S期比例显著增加,诱导细胞凋亡(
P
<
0.05)。DHA可以降低胃癌细胞Dvl2、p-GSK-3β、β-catenin和Cyclin D1的蛋白表达水平(
P
<
0.05),增加GSK-3β蛋白的表达(
P
<
0.05)。同时,SKL2001激活Wnt/β-catenin信号通路,逆转DHA对胃癌细胞迁移和侵袭的抑制作用(
P
<
0.05);XAV939抑制Wnt/β-catenin信号通路,进一步加强DHA对胃癌细胞迁移和侵袭的抑制作用(
P
<
0.05)。
结论
2
DHA能有效抑制胃癌细胞的增殖、侵袭和迁移,阻滞细胞周期停留在S期,诱导胃癌细胞凋亡,其机制可能与抑制Wnt/β-catenin信号通路的激活有关。
Objective
2
To investigate the effect of dihydroartemisinin (DHA) on the proliferation and invasion in gastric cancer cells and its possible molecular mechanism.
Methods
2
Human gastric cancer cell lines BGC-823 and SGC-7901 were exposed to different concentrations of DHA. MTT assay
wound healing assay
Transwell chamber test
and flow cytometry were used respectively to measure the cell proliferation
migration
invasion
and cell cycle distribution and apoptosis. The expression levels of DVL2
GSK-3β
p-GSK-3β
β-catenin and Cyclin D1 were detected by Western blotting.
Results
2
DHA inhibited the proliferation
invasion and migration of BGC-823 and SGC-7901 cells in a concentration-dependent manner (
P
<
0.05). DHA exposure for 48 h significantly increased the percentage of gastric cancer cells at S phase
and induced cell apoptosis (
P
<
0.05). DHA treatment resulted in the decreases in the protein levels of DVL2
p-GSK-3β
β-catenin and Cyclin D1 (
P
<
0.05)
and increase in that of GSK-3β (
P
<
0.05). SKL2001
agonist of the Wnt/β-catenin pathway
reversed the inhibitory effect of DHA on proliferation and invasion of gastric cancer cells (
P
<
0.05)
while the inhibitor
XAV939
enhanced the above effects of DHA (
P
<
0.05).
Conclusion
2
DHA inhibits the proliferation
invasion and migration
arrests the cell cycle at S phase and induces cell apoptosis in gastric cancer cells
which may be associated with its suppression of Wnt/β-catenin signaling pathway.
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