Effects of ABT‑737 combined with irradiation treatment on uterine cervical cancer cells

Shen,Huang‑Pin; Wu,Wen‑Jun; Ko,Jiunn‑Liang; Wu,Tzu‑Fan; Yang,Shun‑Fa; Wu,Chih‑Hsien; Yeh,Chia‑Ming; Wang,Po‑Hui

doi:10.3892/ol.2019.10755

Effects of ABT‑737 combined with irradiation treatment on uterine cervical cancer cells

Authors:
- Huang‑Pin Shen
- Wen‑Jun Wu
- Jiunn‑Liang Ko
- Tzu‑Fan Wu
- Shun‑Fa Yang
- Chih‑Hsien Wu
- Chia‑Ming Yeh
- Po‑Hui Wang
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Affiliations: Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C.
Published online on: August 16, 2019 https://doi.org/10.3892/ol.2019.10755
Pages: 4328-4336

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Abstract

The aim of the present study was to examine the role of ABT‑737, an inhibitor of B‑cell lymphoma 2 (Bcl‑2), in enhancing the effect of irradiation on uterine cervical cancer. Based on The Cancer Genomic Atlas (TCGA), Bcl‑2 mRNA expression was associated with the Tumor‑Node‑Metastasis stage of cervical cancer. Therefore, it was hypothesized that Bcl‑2 inhibition may decrease the progression of cervical cancer. ABT‑737 was added to irradiation treatment to evaluate its effectiveness in inhibiting cancer cell progression. SiHa and CaSki cervical cancer cells were selected for in vitro assays. Patients with advanced stage III uterine cancer had slightly increased mRNA expression levels of Bcl‑2 compared with patients with stage I cancer, although the difference was not significant. ABT‑737 and radiation administration induced a synergistic cytotoxic effect based on the MTT assay and flow cytometry results, where an increase in apoptosis was observed. The apoptotic percentages were significantly increased in the cells treated with a combination of ABT‑737 and irradiation. Loss of mitochondrial membrane potential and gain of reactive oxygen species (ROS) were detected by flow cytometry in CaSki and SiHa cells treated with ABT‑737 and radiation. Additionally, the protein expression levels of the cleaved forms of poly ADP ribose polymerase and caspase‑7 were increased following the combined treatment. In conclusion, ABT‑737 and irradiation may induce apoptosis via loss of mitochondrial membrane potential and a ROS‑dependent apoptotic pathway in CaSki and SiHa cells. The present study indicates that ABT‑737 may be a potential irradiation adjuvant when treating cervical cancer.

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