龙海晨
(2025-03-10 20:43):
#paper Li W, Ma G, Deng Y, Wu Q, Wang Z, Zhou Q. Artesunate exhibits synergistic anti-cancer effects with cisplatin on lung cancer A549 cells by inhibiting MAPK pathway. Gene. 2021 Jan 15;766:145134. doi: 10.1016/j.gene.2020.145134. Epub 2020 Sep 6. PMID: 32898605.这篇文章讲述了青蒿琥酯 (Artesunate,ART)联合顺铂(cisplatin,CIS) 的抗肿瘤作用。青蒿琥酯 (ART) 是一种已在全球范围内广泛用作抗疟疾药物。作者使用肺癌 A549细胞系研究发现,ART 增加剂量或增加时间的方式显着抑制细胞增殖。ART 与顺铂联合使用效果更加明显。与单一处理相比,联合处理显著降低了集落形成率,并增加了 TUNEL 阳性细胞的发生率。机制上,联合处理影响 Bcl-2 、 Bax 、 p-P53 、 Caspase-3/7 、 Caspase-9 、 CyclinB1 、 P34 、 P21 的表达,并协同调节 P38/JNK/ERK1/2 MAPK 通路的活性。
Artesunate exhibits synergistic anti-cancer effects with cisplatin on lung cancer A549 cells by inhibiting MAPK pathway
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Abstract:
BACKGROUND: Artesunate (ART) has been used extensively as anti-malarial drugs worldwide. Besides, it has also been reported to have anti-cancer activities. This study was aimed to explore the anti-cancer activity of ART in combination with cisplatin (CIS) on A549 cells.METHODS: Cells were cultured with different concentrations of ART and/or CIS for 24, 48, or 72 h to test the anti-proliferative effects by CCK-8 assay. Colony formation assay and EdU staining were also performed. TUNEL staining was used to illustrate the morphologic changes. Cell cycle and apoptosis were determined by flow cytometry assay, and Western blot analysis was conducted to detect the expression of apoptosis- and proliferation-related proteins. Caspase activities were determined by colorimetric assay kit. Moreover, the synergistic effect of ART with CIS in A549 cell xenograft model was also determined.RESULTS: ART significantly inhibited cell proliferation in dose- and time-dependent manners. Collectively, the combination treatment remarkably decreased colony formation rates and increased the rates of TUNEL-positive cells compared with mono-treatment. Mechanistically, the combination treatment influenced the expression of Bcl-2, Bax, p-P53, Caspase-3/7, Caspase-9, CyclinB1, P34, P21, and synergistically regulated the activity of P38/JNK/ERK1/2 MAPK pathway. In mice A549 xenograft tumors, the combination strategy significantly increased the anti-cancer efficacy of ART and CIS alone, consistent with the in vitro observations.CONCLUSIONS: ART exhibited significant anti-tumor effect on A549 cells and this efficiency could be enhanced by combination with CIS.
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