Oroxylin a Inhibits the Protection of Bone Marrow Microenvironment on CML Cells Through CXCL12/CXCR4/P-gp Signaling Pathway
Authors: Li Zhao
Wenjun Li
Renxiang Tan
You Zhou
Yue Yang
Hanbo Cao
Yizhou Zhou
Qinglong Guo
Journal: Frontiers in oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: CXCL12/CXCR4; Imatinib (IM); bone marrow environment; oroxylin A; β-catenin/P-gp.
Affiliations: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China., State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, China.

Abstract:  Imatinib (IM) resistance could have significant impact on the survival time of the CML-patients treated with IM. Previous studies have shown that the protective effects of the bone marrow stroma cells (BMSCs) on CML cells are achieved by the secretion of CXCL12. The aim of this study was to investigate whether Oroxylin A could reverse the protective effect of BMSCs on CML cells and illuminate the underlying mechanisms. The results showed that CXCL12 could enhance the resistance potential of K562 and KU812 cells to IM by increasing the expression of CXCR4, thus promoting the translocation of β-catenin into nucleus and subsequently increasing the expression of P-gp in K562 and KU812 cells. What's more, IM resistance could also be partially reversed by CXCR4 siRNA transfection. Moreover, the reverse effect of IM resistance by Oroxylin A was demonstrated by the inhibition of β-catenin/P-gp pathway via the decrease of CXCR4 in vitro. The in vivo study also showed that Oroxylin A could decrease the expression of P-gp and β-catenin in mice bone marrow with low toxicity, which could be consistent with the mechanisms verified in vitro studies. In conclusion, all these results showed that Oroxylin A improved the sensitivity of K562 and KU812 cells to IM in BM microenvironment by decreasing the expression of CXCR4 and then inhibiting β-catenin/P-gp pathway. 

Retracted: No

PubPeer comments:
 two panels in figure 3H appear to be same images, however they are from different cells (K562 Ku812). ![file] , 
 #1 Corrigendum published 27 September 2019: In the original article, there was a mistake in Figure 3H as published. Due to carelessness, the picture of the u201ck562-indo groupu201d was accidentally placed in the u201cku812-indo groupu201d. The corrected Figure 3H appears below. ![] , 
 Another minor corrigendum might be helpful. Here are Figures 1C and 4C. It is clear from the text that Fig 1 is illustrating *part* of a larger experiment, described later and illustrated by Fig 4. For narrative reasons, the authors describe the Oroxylin condition in Fig 4 as an afterthought or postscript to Fig 1, but it is clear from the repeated results that the larger, combined experiment came first. ![file] So most of the bands in Fig 4C are the same as in 1C (with an additional lane, for Oroxylin)... except for the Actin band in the KU812 panel. One of the two Figures is in error. , 
 Many of problematic issues in Qinglong Guo s publications may look harmless separately, but when you see the long list of similar problems in many papers, some alarm bells should ring. I hope that both CPU and the publishers show their responsibility, especially since clinical trials have been initiated or planned based on work done by these researchers. , 
 11111111111111111 , 
 2020 retraction. https: www.frontiersin.org articles 10.3389 fonc.2020.00714 full Frontiers Editorial Office* A Retraction of the Review Article Oroxylin a Inhibits the Protection of Bone Marrow Microenvironment on CML Cells Through CXCL12 CXCR4 P-gp Signaling Pathway by Cao, H., Li, W., Zhou, Y., Tan, R., Yang, Y., Zhou, Y., et al. (2019). Front. Oncol. 9:188. doi: 10.3389 fonc.2019.00188 The journal retracts the 03 April 2019 article cited above. Following publication, concerns were raised regarding the integrity of western blot images. An investigation was therefore conducted in accordance with our established procedures, revealing that image duplication had taken place. The authors failed to provide satisfactory raw data and requested to have this article retracted. This retraction was approved by the Chief Editors of Frontiers in Oncology and the Editor-in-Chief of Frontiers. The authors concur with the retraction and sincerely regret any inconvenience this may have caused to the reviewers, editors, and readers of Frontiers in Oncology ,