Li Y, Zhao ZG, Luo Y, Cui H, Wang HY, Jia YF, Gao YT. Dual targeting of Polo-like kinase 1 and baculoviral inhibitor of apoptosis repeat-containing 5 in TP53-mutated hepatocellular carcinoma. World J Gastroenterol 2020; 26(32): 4786-4801 [PMID: 32921957 DOI: 10.3748/wjg.v26.i32.4786]
Corresponding Author of This Article
Ying-Tang Gao, PhD, Professor, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Nankai University Affiliated Third Center Hospital, No. 83, Jintang Road, Hedong District, Tianjin 300170, China. gaoyt816@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Yan Li, Zhen-Gang Zhao, Hao Cui, Hao-Yu Wang, Department of Hepatology, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
Yin Luo, Ying-Tang Gao, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Nankai University Affiliated Third Center Hospital, Tianjin 300170, China
Yan-Fang Jia, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Medical University Third Center Clinical College, Tianjin 300170, China
Author contributions: Li Y, Zhao ZG, Luo Y, and Jia YF performed the majority of experiments and analyzed the data; Cui H and Wang HY were responsible for animal experiments; Li Y and Gao YT designed and coordinated the research; Li Y, Luo Y, and Gao YT wrote the paper; all authors approved the final version of the article.
Supported by National Science and Technology Major Project, No. 2018ZX10732-202-004; Tianjin Science and Technology Plan Project, No. 17JCYBJC26100 and No. 19ZXDBSY00030.
Institutional review board statement: This study/paper was reviewed and approved by the Ethics Committee of Tianjin Third Central Hospital.
Institutional animal care and use committee statement: All animal experiments and procedures were conducted under the protocol approved by the Animal Care and Use Committee of Nankai University.
Conflict-of-interest statement: All authors have nothing to disclose.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ying-Tang Gao, PhD, Professor, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Nankai University Affiliated Third Center Hospital, No. 83, Jintang Road, Hedong District, Tianjin 300170, China. gaoyt816@163.com
Received: May 7, 2020 Revised: June 4, 2020 Accepted: August 4, 2020 Published online: August 28, 2020 Processing time: 113 Days and 12.1 Hours
Core Tip
Core tip: A bioinformatics analysis using a TCGA hepatocellular carcinoma (HCC) dataset revealed that Polo-like kinase 1 (PLK1) and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) were overexpressed in the same patient subset and their expression was highly correlated. Overexpression of both PLK1 and BIRC5 was more frequently detected in HCC with p53 mutations. High PLK1 or BIRC5 expression significantly correlated with poor clinical outcome. The PLK1 inhibitors volasertib and GSK461364 or BIRC5 inhibitor YM155 selectively targeted Huh7 cells with mutated p53, but not HepG2 cells with wild-type p53. Combination treatment with volasertib and YM155 synergistically inhibited the viability of Huh7 cells by inducing apoptosis. The efficacy of volasertib and YM155, alone or in combination, was validated in vivo in a Huh7-derived xenograft model in immuno-deficient NSIG mice.
