RETRACTED: FL118 inhibits viability and induces apoptosis of colorectal cancer cells via inactivating the CIP2A/PP2A axis
Authors: Xiaoyi Zhang
Ailing Zhang
Xuezhu Lin
Mingquan Gao
Guohui Jiang
Hui Gao
Zhihong Yang
Quanzhong Su
Jingjie Tong
Journal: Life Sciences (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CIP2A; CRC; Camptothecin; FL118; PP2A.
Affiliations: Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266021, Shandong Province, China., Sichuan Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, Sichuan Province, China., Qingdao Hiser hospital, Qingdao 266033, Shandong Province, China., Department of school infirmary, Qingdao University, Qingdao 266021, Shandong Province, China., Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266021, Shandong Province, China. Electronic address: .

Abstract:  Aims: FL118, a novel camptothecin analogue, has been extensively studied for its superior antitumor potency. The aim of this research study is to explore its potential mechanism of action in anti- colorectal cancer (CRC). Main methods: The effect of FL118 on CRC cell proliferation was assessed using CCK-8 assay, while apoptosis was detected using Hoechst staining and Flow cytometry assays. The expression levels of CIP2A were analyzed using qRT-PCR. The expression of CIP2A, PP2A-C, Bax, cleaved caspase-3 and PARP were analyzed using western blotting analysis. The expressions of related proteins in CRC tissues were detected using immunohistochemical staining. TUNEL assay was used to detect apoptosis of tissue. Toxicity of FL118 in primary organs were examined using H&amp;E staining. Key findings: The results show that FL118 can inhibit the proliferation and clonogenic potential of CRC cells and increase the expression of pro-apoptosis proteins, Bax, cleaved caspase-3 and PARP. Microarray analyses found that FL118 treatment significantly decreases cancerous inhibition of protein phosphatase 2A (CIP2A). Further validation found that CIP2A is aberrantly upregulated in CRC tissues, and is positively correlated with the progression of CRC. In vitro findings confirm that FL118 mediates the downregulation of CIP2A, at both protein and mRNA levels. Co-treatment with Okadaic acid (OA) (a PP2A inhibitor) partially abolishes the anti-proliferative and pro-apoptotic effect of FL118. Consistently, in vivo experiment demonstrates that FL118 can effectively suppress tumorigenesis without any obvious toxic effects. Significance: Collectively, these findings exhibit the anti-neoplastic effects of FL118 against CRC through the down regulation of CIP2A, which subsequently enhances the activity of PP2A. 

Retracted: Yes

PubPeer comments:
 I hope people appreciate the effort put into creating this montage. From top left, clockwise: 6F from [Lin et al (2019)] :  The toxicity of FL118 on the heart, liver, spleen, lung and kidneys were examined using H E staining . 6F [Wang et al (2019)] :  Soy B did not cause marked histological damage in spleen, liver, heart, kidney and lung tissue . 7H [Niu et al (2019)] :  HE staining was applied to evaluate the changes in the lung, heart, kidney and liver tissues . 7F [Li et al (2019)] :  Representative pictures of H E stained tissues of the heart, liver, spleen, lung and kidney of the AIF-treated mice .  In the  kidney column for Lin et al, the three panels are in the opposite sequence from the Wang et al and Niu et al kidney columns. To show that would require more colors. , 
 Fig 5D.  Analysis of apoptotic cell ratio using flow cytometry, following Annexin-FITC PI staining . The panels here are repeated frequently (differently labeled) across this corpus of papers. Picking an example for comparison at random from the files I have open at the moment, below is 4B from [Wang et al (2019)] .  , 
 Fig 1D.  Following incubation with FL118 (0, 10, and 20 nM) for 14 days, the numbers of colonies of HCT-116 and SW480 cells were quantified using colony formation assay . After vertical flips, two of the colony plates are unexpectedly similar to Fig 1(d) of [Wang et al (2019)] (at right),  Soy B suppressed the proliferation of ccRCC cells.  , 
 #3 Other colony plates of 1D appear to be repeated from Fig 2D from [Han et al (2016)] :  MiR-370 functions as a tumor suppressor in ESCC cells. ... D. Mi-370 mimic suppresses cell proliferation, while miR-370 inhibitor promotes cell growth.  , 
 #3 There it is again! Fig 3B from [Wang et al (2017)] :  The promoting effect of anti-miR-101 on cell growth and invasion. ... B. Anti-miR-101 enhances long term cell proliferation.   , 
 2020 retraction. https: www.sciencedirect.com science article pii S0024320520307736?via%3Dihub This article has been retracted: please see Elsevier Policy on Article Withdrawal . This article has been retracted at the request of the Editor-in-Chief. Colony plates from Fig. 1D appear similar to colony plates from Fig. 1(d) (after vertical flipping) of the article published by Luping Wang, Junyu Wang, Hong Zhao, Guoping Jiang, Xiaojie Feng, Wenxia Sui and Hongling Liu in Naunyn-Schmiedeberg s Archives of Pharmacology 392 (2019) 551u2013563 https: doi.org 10.1007 s00210-018-01607-w 8 comments on PubPeer (by: Hoya Camphorifolia, Elisabeth M Bik) , Fig. 2D of the article published by the corresponding author Hui Gao et al. in the American Journal of Cancer Research 6 (2016) 2755u20132771 http: www.ajcr.us files ajcr0039673.pdf and Fig. 3B of the article published by Tingting Wang, Yuhua Jiang, Lei Chu, Tianhui Wu and Jie You in the American Journal of Cancer Research 7 (2017) 999u20131015 http: www.ajcr.us files ajcr0048620.pdf. Panels from Fig. 5D appear similar to panels from Fig. 4B of the article published by Luping Wang, Lu Yun, Xiaojun Wang, Liying Sha, Luning Wang, Yingying Sui and Hui Zhang in Life Sciences 218 (2019) 16u201324 https: doi.org 10.1016 j.lfs.2018.12.023 5 comments on PubPeer (by: Hoya Camphorifolia) . Panels from Fig. 6F appear similar to panels from Fig. 6F of the article published by Luping Wang, Lu Yun, Xiaojun Wang, Liying Sha, Luning Wang, Yingying Sui and Hui Zhang in Life Sciences 218 (2019) 16u201324 https: doi.org 10.1016 j.lfs.2018.12.023, Fig. 7H of the article published by Ying Niu, Jinping Zhang, Yalin Tong, Jiansheng Li and Bingrong Liu in Life Sciences 237 (2019) 116893 https: doi.org 10.1016 j.lfs.2019.116893 10 comments on PubPeer (by: Hoya Camphorifolia) and Fig. 7F of the article published by Dong Li, Xiaoyan Li, Genqu Li, Yan Meng, Yanghong Jin, Shuang Shang and Yanjie Li in Life Sciences 216 (2019) 259u2013270 https: doi.org 10.1016 j.lfs.2018.11.032. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process. ,