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Artesunate promotes cervical cancer cell apoptosis by regulating Bcl2 family molecules and reducing the mitochondrial membrane potential

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机构: [1]Department of Gynaecological Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China. [2]Department of Flow Cytometry, Tumour Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China. [3]Department of Molecular Biology, Tumour Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
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关键词: cervical cancer ART mitochondrial membrane potential reactive oxygen species calcium ions Bcl2 family cell apoptosis

摘要:
Artesunate (ART), an antimalarial drug, has a broad spectrum of antitumour effects in cancer types such as esophageal and gastric cancer. However, evidence demonstrating the role of ART in cervical cancer cells is limited. In the present study, the inhibitory effect of ART on the growth of cervical cancer cells through the modulation of the cell cycle and apoptosis was investigated. The growth-inhibitory effect of ART on a cervical cancer cell line (SiHa) was detected using a Cell Counting Kit-8 assay after treatment with ART for 24 h, after which the half-maximal inhibitory concentration (IC50) was calculated. Using flow cytometry assays, apoptosis, the cell cycle, the levels of reactive oxygen species (ROS) and calcium (Ca2+) ions, as well as the mitochondrial membrane potential were evaluated in SiHa cells following treatment with ART for 24 and 48 h. The mRNA expression levels of Bcl2, Bcl-xl, (myeloid cell leukaemia 1) Mcl-1, Bcl2-like protein 11 (BIM), (Bcl2-related ovarian killer protein) Bok, Bax and (Bcl2 homologous antagonist/killer) Bak in SiHa cells were detected using reverse transcription-quantitative PCR. ART inhibited the growth of SiHa cells in a dose-dependent manner. The IC50 of ART in SiHa cells was 26.32 µg/ml. According to the IC50 value, 15, 30 and 100 µg/ml ART were selected for further experiments, and normal saline (0 µg/ml ART) was used as the control group. The results indicated that treatment with 15, 30 and 100 µg/ml ART for 24 and 48 h induced apoptosis, increased the levels of ROS, the levels of Ca2+ and the mRNA expression levels of BIM, Bok, Bax and Bak, but decreased the cell proliferation indices, the mitochondrial membrane potential and the mRNA expression levels of Bcl2, Bcl-xl and Mcl-1 in a dose- and time-dependent manner. In conclusion, ART inhibited the growth of SiHa cells and induced apoptosis via a mechanism associated with the regulation of Bcl2 family member expression, which was associated with the increase of the levels of ROS and Ca2+ and the reduction of the mitochondrial membrane potential.Copyright: © 2024 Zhang et al.

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出版当年[2025]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
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Q3 ONCOLOGY
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Q3 ONCOLOGY

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第一作者机构: [1]Department of Gynaecological Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
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通讯机构: [2]Department of Flow Cytometry, Tumour Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
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