Kaempferol inhibits proliferation, migration, and invasion of liver cancer HepG2 cells by down-regulation of microRNA-21
Authors: Yang Yan
Xiaopeng Hong
Haijing Li
Zhidong Lin
Xialei Liu
Genglong Zhu
Journal: International Journal of Immunopathology and Pharmacology (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: PI3K/AKT/mTOR signaling pathway; kaempferol; liver cancer; microRNA-21; phosphatase and tensin homologue.
Affiliations: 1 Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China., 2 Department of Central Supply Service, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China., 3 Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China., 4 Department of General Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.

Abstract:  Liver cancer is one of the most common and lethal cancers in human digestive system, which kills more than half a million people every year worldwide. This study aimed to investigate the effects of kaempferol, a flavonoid compound isolated from vegetables and fruits, on hepatic cancer HepG2 cell proliferation, migration, invasion, and apoptosis, as well as microRNA-21 (miR-21) expression. Cell viability was detected using cell counting kit-8 (CCK-8) assay. Cell proliferation was measured using 5-bromo-2'-deoxyuridine (BrdU) incorporation assay. Cell apoptosis was assessed using Guava Nexin assay. Cell migration and invasion were determined using two-chamber migration (invasion) assay. Cell transfection was used to change the expression of miR-21. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyze the expressions of miR-21 and phosphatase and tensin homologue (PTEN). Expression of key proteins involved in proliferation, apoptosis, migration, invasion, and phosphatidylinositol 3-kinase/protein kinase 3/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway were evaluated using western blotting. Results showed that kaempferol significantly inhibited HepG2 cell proliferation, migration, and invasion, and induced cell apoptosis. Kaempferol remarkably reduce the expression of miR-21 in HepG2 cells. Overexpression of miR-21 obviously reversed the effects of kaempferol on HepG2 cell proliferation, migration, invasion, and apoptosis. Moreover, miR-21 negatively regulated the expression of PTEN in HepG2 cells. Kaempferol enhanced the expression of PTEN and inactivated PI3K/AKT/mTOR signaling pathway in HepG2 cells. In conclusion, kaempferol inhibited proliferation, migration, and invasion of HepG2 cells by down-regulating miR-21 and up-regulating PTEN, as well as inactivating PI3K/AKT/mTOR signaling pathway. 

Retracted: No

PubPeer comments:
 This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels. Despite these similarities, these papers are authored by researchers from different departments and institutes, with almost no overlap in authors. The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing A more detailed description of this set of papers, suspected to all be generated by a common source, a paper mill , can be found here: * https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) * https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The same paper mill has been described in these papers: * Jana Christopher - Systematic fabrication of scientific images revealed - FEBS Letters (2018) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13201 * Jennifer A Byrne and Jana Christopher - Digital magic, or the dark arts of the 21st centuryu2014how can journals and peer reviewers detect manuscripts and publications from paper mills? - FEBS Letters (2020) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13747 , 
 February 2021 Expression of Concern: https: journals.sagepub.com doi 10.1177 20587384211000844 It reads:  *It has been brought to SAGEu2019s attention that this article may have been written (and possibly submitted) by a third-party agency, and that the contents of the article may be partially or wholly fabricated. SAGE is currently conducting a thorough investigation into this to establish the most appropriate way forward.* , 
 An example of the tadpole Western Blots in this paper- Fig 7. ![file] , 
 Retracted [2 September 2021] . H t [RetractionWatch] . ------------------------- At the request of the Journal Editor(s) the following article has been retracted. Zhu G, Liu X, Li H, Yan Y, Hong X, Lin Z (2018) Kaempferol inhibits proliferation, migration, and invasion of liver cancer HepG2 cells by down-regulation of microRNA-21. International Journal of Immunopathology and Pharmacology 32: 1-12. DOI: 10.1177 2058738418814341. Significant similarities between this paper and a number of other papers have been identified, as well as indication of image and data manipulation suggestive of the use of a u201cpaper millu201d. These papers share common structures and wording yet do not share any common authors. The authors did not provide a sufficient response or evidence to refute these claims. As a result, the scientific accuracy of this paper is not reliable. Adhering to the international guidelines established by the Committee on Publication Ethics, the Journal has determined these are grounds for retraction. , 
 Via http: www.most.gov.cn zxgz kycxjs kycxgzdt 202203 t20220318_179892.html u3000u300010. The paper  Kaempferol inhibits proliferation, migration, and invasion of liver cancer HepG2 cells by down-regulation of microRNA-21 with Lin Zhidong as the corresponding author and Zhu Genglong as the first author of the Fifth Affiliated Hospital of Sun Yat-sen University. After investigation, it was found that the paper had ghostwriting and falsification of research data. Lin Zhidong will be dealt with as follows: he will cancel his professional title for promotion, apply for scientific and technological plans (special projects, funds, etc.), and evaluate his qualifications for 5 years. The post grade is lowered by one level; Zhu Genglong will be dealt with as follows: cancel the postgraduate tutor qualifications, not hire teachers, cancel the promotion title, apply for scientific and technological plans (special projects, funds, etc.) projects, assessment and other qualifications for 7 years, cancel the deputy Qualifications for professional and technical positions of chief physicians, stay on party probation for 1 year, and lower the post grade by one level. u3000u3000(Notification link: http: xuefeng.sysu.edu.cn gzdt 1398704.htm) ,