FK228 sensitizes radioresistant small cell lung cancer cells to radiation
文献类型：期刊论文
| 作者 | Li, Hong1,3 ; Ma, Liying1,2,3; Bian, Xing1,2,3; Lv, Yang1,2,3; Lin, Wenchu1,3
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| 刊名 | CLINICAL EPIGENETICS
 |
| 出版日期 | 2021-02-25 |
| 卷号 | 13 |
| ISSN号 | 1868-7075 |
| 关键词 | Small cell lung cancer FK228 Histone deacetylase PI3K Radioresistance DNA damage repair |
| DOI | 10.1186/s13148-021-01025-5 |
| 通讯作者 | Lin, Wenchu(wenchu@hmfl.ac.cn) |
| 英文摘要 | BackgroundConcurrent thoracic radiation plus chemotherapy is the mainstay of first-line treatment for limited-stage small cell lung cancer (LS-SCLC). Despite initial high responsiveness to combined chemo- and radiotherapy, SCLC almost invariably relapses and develops resistance within one year, leading to poor prognosis in patients with LS-SCLC. Developing new chemical agents that increase ionizing radiation's cytotoxicity against SCLC is urgently needed.ResultsDual histone deacetylase (HDAC) and PI3K inhibitor FK228 not only displayed potent anticancer activity, but also enhanced the therapeutic effects of radiotherapy in SCLC cells. Mechanistically, radioresistant SCLC cells exhibit a lower level of histone H3K9 acetylation and a higher expression level of the MRE11-RAD50-NBS1 (MRN) complex and show more efficient and redundant DNA damage repair capacities than radiosensitive SCLC cells. FK228 pretreatment resulted in marked induction of H3k9 acetylation, attenuated homologous recombination (HR) repair competency and impaired non-homologous end joining (NHEJ) repair efficacy, leading to the accumulation of radiation-induced DNA damage and radiosensitization.ConclusionThe study uncovered that FK228 sensitized human radioresistant SCLC cells to radiation mainly through induction of chromatin decondensation and suppression of DNA damage signaling and repair. Our study provides a rational basis for a further clinical study to test the potential of FK228 as a radiosensitizing agent to increase the radiation-induced tumor cell kill in LS-SCLC patients. |
| 资助项目 | National Natural Science Foundation of China[81972191] ; National Natural Science Foundation of China[81672647] ; Science and Technology Major Project of Anhui Province[18030801140] ; Key program of 13th five-year plan of CASHIPS[KP-2017-26] ; 100-Talent Program of Chinese Academy of Sciences ; High Magnetic Field Laboratory of Anhui Province |
| WOS研究方向 | Oncology ; Genetics & Heredity |
| 语种 | 英语 |
| 出版者 | BMC |
| WOS记录号 | WOS:000624393700001 |
| 资助机构 | National Natural Science Foundation of China ; Science and Technology Major Project of Anhui Province ; Key program of 13th five-year plan of CASHIPS ; 100-Talent Program of Chinese Academy of Sciences ; High Magnetic Field Laboratory of Anhui Province |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/120475]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Lin, Wenchu |
| 作者单位 | 1.Chinese Acad Sci, Hefei Inst Phys Sci, High Field Magnet Lab, Hefei 230031, Anhui, Peoples R China 2.Univ Sci & Technol China, Hefei 230026, Anhui, Peoples R China 3.Chinese Acad Sci, Hefei Inst Phys Sci, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei 230031, Anhui, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Hong,Ma, Liying,Bian, Xing,et al. FK228 sensitizes radioresistant small cell lung cancer cells to radiation[J]. CLINICAL EPIGENETICS,2021,13. |
| APA | Li, Hong,Ma, Liying,Bian, Xing,Lv, Yang,&Lin, Wenchu.(2021).FK228 sensitizes radioresistant small cell lung cancer cells to radiation.CLINICAL EPIGENETICS,13. |
| MLA | Li, Hong,et al."FK228 sensitizes radioresistant small cell lung cancer cells to radiation".CLINICAL EPIGENETICS 13(2021). |
入库方式： OAI收割
来源：合肥物质科学研究院
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