Lysophosphatidic acid protects cervical cancer HeLa cells from apoptosis induced by doxorubicin hydrochloride

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Authors
Wang, Xibo
Wang, Haihua
Mou, Xiaoxiao
Xu, Yilin
Han, Wenbo
Huang, Aimin
Li, Yanwei
Jiang, Hui
Yang, Xiaoyun
Hu, Zhenbo
Issue Date
2022-06-17
Type
Article
Language
en_US
Keywords
Lysophosphatidic Acid , Doxorubicin Hydrochloride , Cervical Cancer , Apoptosis , Reactive Oxygen Species
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Abstract
Cervical cancer is one of the most common types of gynecological tumors. Lysophosphatidic acid (LPA), as a bioactive lipid medium, plays an important role in numerous physiological and pathophysiological processes, including the stimulation of cell migration and tumor cell invasion. LPA is increased in the plasma of patients with cervical cancer. Doxorubicin hydrochloride (DOX) is used as a first-line drug in the treatment of cervical cancer in clinics, however, the effect and molecular mechanism of LPA on DOX-induced apoptosis in cervical cancer cells remain unclear. Therefore, the present study aimed to explore the effect and underlying molecular mechanism of LPA on DOX-induced apoptosis in cervical cancer cells. HeLa cells were treated as a control group or with LPA (10 µmol/l), DOX (4 µmol/l) or LPA (10 µmol/l) + DOX (4 µmol/l) for 24 h. Using transmission electron microscopy the results demonstrated that LPA reduced cell death and the degree of chromatin aggregation in DOX-induced HeLa cells. Reverse transcription-quantitative PCR demonstrated that LPA significantly downregulated caspase-3 mRNA expression levels in DOX-induced HeLa cells. Moreover, western blotting demonstrated that LPA significantly reduced caspase-3 and cleaved caspase-3 protein expression levels in DOX-induced HeLa, C33A and SiHa cells. Furthermore, flow cytometry demonstrated that LPA may prevent apoptosis in DOX-induced HeLa cells (P<0.05). Using dichloro-dihydro-fluorescein diacetate assay, it was demonstrated that LPA significantly reduced the intracellular ROS levels induced by DOX. In summary, the present study indicated that LPA may protect HeLa cells from apoptosis induced by DOX. These findings have provided experimental evidence that LPA may be a potential therapeutic target for the treatment of cervical cancer.
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Wang, X., Wang, H., Mou, X., Xu, Y., Han, W., Huang, A., Li, Y., Jiang, H., Yang, X., & Hu, Z. (2022). Lysophosphatidic acid protects cervical cancer HeLa cells from apoptosis induced by doxorubicin hydrochloride. Oncology letters, 24(2), 267. https://doi.org/10.3892/ol.2022.13387
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Oncology Letters
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