TNKS inhibitors potentiate proliferative inhibition of BET inhibitors via reducing beta-Catenin in colorectal cancer cells
文献类型：期刊论文
| 作者 | Wu, Qian1,2; Xuan, Yi-Fei1,2; Su, Ai-Ling1,2; Bao, Xu-Bin1; Miao, Ze-Hong1,2; Wang, Ying-Qing1,2
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| 刊名 | AMERICAN JOURNAL OF CANCER RESEARCH
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| 出版日期 | 2022 |
| 卷号 | 12期号:3页码:1069-+ |
| 关键词 | BET inhibitor Tankyrases inhibitor beta-Catenin antitumor activity combination therapy |
| ISSN号 | 2156-6976 |
| 通讯作者 | Miao, Ze-Hong(zhmiao@simm.ac.cn) ; Wang, Ying-Qing(yqwang@simm.ac.cn) |
| 英文摘要 | Colorectal cancer (CRC) is an aggressive malignancy with limited options for treatment. Targeting the bromodomain and extra terminal domain (BET) proteins by using BET inhibitors (BETis) could effectively interrupt the interaction with acetylated histones, inhibit genes transcription and have shown a certain effect on CRC inhibition. To improve the efficacy, the inhibitors of Tankyrases, which cause accumulation of AXIN through dePARsylation, in turn facilitate the degradation of beta-Catenin and suppress the growth of adenomatous polyposis coli (APC)-mutated CRCs, were tested together with BETi as a combination treatment. We examined the effects of BETi and Tankyrases inhibitor (TNKSi) together on the proliferation, cell cycle and apoptosis of human CRCs cell lines with APC or CTNNB1 mutation, and elucidated the underlying molecular mechanisms affected by the double treatment. The result showed that the TNKSi could sensitize all tested CRC cell lines to BETi, and the synergistic effect was not only seen in cell proliferation inhibition, but also confirmed in decreased colony-forming ability and weaken EdU incorporation compared with monotherapy. Combined treatment resulted in enhanced G1 cell cycle arrest and increased apoptosis. In addition, we found beta-Catenin was potentially inhibited by the combination and revealed that both BETi-induced transcriptional inhibition and TNKSi-mediated protein degradation all reduced the beta-Catenin accumulation. In all, the synergistic effects suggest that combination of BETi and TNKSi could provide novel treatment opportunities for CRC, but both TNKSi and combination strategy need to be optimized. |
| WOS关键词 | TANKYRASE INHIBITORS ; COMBINATION ; BROMODOMAIN |
| 资助项目 | Science and Technology Commission of Shanghai Municipality[19ZR1467900] ; Science and Technology Commission of Shanghai Municipality[20ZR1468100] ; Nova Development Program of the Shanghai Insti-tute of Materia Medica ; Chinese Academy of Sciences ; State Key Laboratory of Drug Research |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000777981400010 |
| 出版者 | E-CENTURY PUBLISHING CORP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/299863]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Miao, Ze-Hong; Wang, Ying-Qing |
| 作者单位 | 1.Chinese Acad Sci, Canc Res Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Qian,Xuan, Yi-Fei,Su, Ai-Ling,et al. TNKS inhibitors potentiate proliferative inhibition of BET inhibitors via reducing beta-Catenin in colorectal cancer cells[J]. AMERICAN JOURNAL OF CANCER RESEARCH,2022,12(3):1069-+. |
| APA | Wu, Qian,Xuan, Yi-Fei,Su, Ai-Ling,Bao, Xu-Bin,Miao, Ze-Hong,&Wang, Ying-Qing.(2022).TNKS inhibitors potentiate proliferative inhibition of BET inhibitors via reducing beta-Catenin in colorectal cancer cells.AMERICAN JOURNAL OF CANCER RESEARCH,12(3),1069-+. |
| MLA | Wu, Qian,et al."TNKS inhibitors potentiate proliferative inhibition of BET inhibitors via reducing beta-Catenin in colorectal cancer cells".AMERICAN JOURNAL OF CANCER RESEARCH 12.3(2022):1069-+. |
入库方式： OAI收割
来源：上海药物研究所
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