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Article type: Short Communication
Authors: Li, Honga; b | Wang, Huoganga; b | Deng, Kea; b | Han, Weic | Hong, Boa; b; c; * | Lin, Wenchua; b; *
Affiliations: [a] High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui, China | [b] Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China | [c] Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Correspondence: [*] Corresponding authors: Wenchu Lin, Bo Hong, High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui 230031, China. Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China. E-mail: wenchu@hmfl.ac.cn/bhong@hmfl.ac.cn.
Abstract: BACKGROUND: Cisplatin-based chemotherapy and radiotherapy are the most commonly used treatments for small cell lung cancer (SCLC). However, despise initially dramatic response, the response duration of SCLC patients is variable and resistance to chemo- and radio-therapy inevitably develops. OBJECTIVE: The aim of the study is to investigate the role of Bcl-2 family proteins in predicting SCLC sensitivity to cisplatin treatment, and to identify the potential sensitizer of cisplatin or ratiation treatment in SCLC. METHODS: We collected cisplatin sensitivity data from public available database, and evaluated its possible association with mRNA or protein expression of Bcl-2 family members in SCLC cell lines. RESULTS: The IC50 value of cisplatin was significantly correlated with the ratio of Bcl-2/Bim mRNA expression in 33 SCLC cell lines (P= 0.041) as well as the ratio of Bcl-2/Bim protein expression in 7 SCLC cell lines (P= 0.0252). Furthermore, a BH3-mimetic ABT-263 was found to be able to sensitize SCLC cells to cisplatin or radiation. The synergistic and additive antitumor activity of ABT-263 combined with cisplatin or radiation was associated with the enhanced apoptosis, which may be caused by the disruption of Bcl-2 binding to Bim by ABT-263. CONCLUSIONS: Our study indicates that the ratio of Bcl-2/Bim could be a SCLC response predictor to cisplatin, and ABT-263 addition could be an effective strategy to improve the activity of chemo- or radio-therapy in SCLC.
Keywords: Small cell lung cancer, Bcl-2, Bim, ABT-263, cisplatin, radiation
DOI: 10.3233/CBM-181692
Journal: Cancer Biomarkers, vol. 24, no. 1, pp. 51-59, 2019
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