Synergistic tumor inhibition of colon cancer cells by nitazoxanide and obeticholic acid, a farnesoid X receptor ligand
Authors: Wei Zhao
Junhui Yu
Kui Yang
Xuejun Sun
Jianbao Zheng
Journal: Cancer Gene Therapy (2021)
Discipline: CLINICAL MEDICINE
Keywords: FXR; colorectal tumorigenesis; β-catenin; OCA; drug combinations

Abstract:  The tumor-suppressive role of Farnesoid X receptor (FXR) in colorectal tumorigenesis supports restoring FXR expression as a novel therapeutic strategy. However, the complicated signaling network and tumor heterogeneity hinder the effectiveness of FXR agonists in the clinical setting. These difficulties highlight the importance of identifying drug combinations with potency and specificity to enhance the antitumor effects of FXR agonists. In this study, we found that the β-catenin level affected the antitumor effects of the FXR agonist OCA on colon cancer cells. Mechanistic studies identified a novel FXR/β-catenin complex in colon cancer cells. Furthermore, the depletion of β-catenin expedited FXR nuclear localization and enhanced its occupancy of the SHP promoter and thereby sensitized colon cancer cells to OCA. Furthermore, we utilized a drug combination study and identified that the antiparasitic drug nitazoxanide (NTZ) abrogated β-catenin expression and acted synergistically with OCA in colon cancer cells. The combination of OCA plus NTZ exerts synergistic tumor inhibition in CRC both in vitro and in vivo by cooperatively upregulating SHP expression. In conclusion, our study offers useful evidence for the clinical use of FXR agonists combined with β-catenin inhibitors in combating CRC. 

Retracted: No

PubPeer comments:
 Retracted [4 February 2020] :  The Editors-in-Chief have retracted this article [1] because it significantly overlaps with an article by different authors [2] that was simultaneously under consideration at another journal. The article also showed evidence of authorship manipulation. In addition, the identity of the corresponding author could not be verified: Hasselt University have confirmed that Costanza T Viouonu has not been affiliated with their institution. The authors have not responded to any correspondence about this retraction. Here [2] is Huang, B., Wang, J., Zylbersztejn, M.H.: An extension of the estimation for solutions of certain Laplace equations. J. Inequal. Appl. 2016, 167 (2016). https: journalofinequalitiesandapplications.springeropen.com articles 10.1186 s13660-016-1109-x https: pubpeer.com publications CCBC6F5FD487CAF37F65E253A7A21D Ref [5] in the text is Pang, S, Ychussie, B:  Matsaev type inequalities on smooth cones . J. Inequal. Appl. 2015, Article ID 108 (2015). [Since retracted for plagiarism and fictitious authorship] . , 
 **Decision on handling misconduct cases investigated and handled in 2021 (third batch)** https: www.nsfc.gov.cn publish portal0 tab434 info81957.htm This paper is discussed among the 22 handling decisions announced by the National Natural Science Foundation of China u201cthat have been criticized for notification are now published.u201d (Google Translate). , 
 #2 **Regarding the existence of subrogation and submission in the retracted papers such as Xie Xiaozhen, Handling decisions on issues such as the author of a fictitious paper** National Science and Technology Supervision Office (2021) No. 123 The Supervision Committee of the National Natural Science Foundation of China has retracted the paper  Xie Xiaozhen, Viouonu Costanza.T*. Some new results on the boundary behaviors of harmonic functions with integral boundary conditions. Boundary Value Problems, 2016, 136.  (Marked with fund number 61401368) was investigated for alleged academic misconduct. After investigation, Xie Xiaozhen, the first author of the above-mentioned paper, commissioned a third-party company to write and invest on his behalf. The third-party company also fabricated the corresponding author in the process. Xie Xiaozhen is fully responsible for the above-mentioned problems. After deliberation at the 10th meeting of the 5th Supervisory Committee of the National Natural Science Foundation of China (Comprehensive Professional Committee), the National Natural Science Foundation of Article 2, Paragraph 3, Article 33,  Measures of the National Natural Science Foundation of China Supervisory Committee on Handling Misconduct in the Funding of Science Funds (Trial) Article 17, Paragraph 4, revoke Xie Xiaozhen National Natural Science The National Natural Science Foundation of China project  Scaling Conversion of Multi-source Agricultural Remote Sensing Data (approval number 61401368), to recover the allocated funds, and cancel Xie Xiaozhen s national natural science fund project application qualification for 5 years (July 20, 2021 to July 19, 2026) ), give Xie Xiaozhen a circular and criticize. National Natural Science Foundation of China September 22, 2021 ,