Andrographolide suppress tumor growth by inhibiting TLR4/NF-Œ∫B signaling activation in insulinoma
Authors: Tian Lan
Xuesong Yang
Qian-Qian Zhang
Cui-Ling Qi
Jiang-Chao Li
Yi Ding
Yan Lei
Ping Gong
Li-Jing Wang
Xiao-Dong He
Jian-Guo Geng
Journal: International journal of biological sciences (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Andrographolide; growth.; insulinoma.
Affiliations: 1. Vascular Biology Research Institute, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China., 3. Department of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College of Jinan University, Guangzhou 510632, China., 2. Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.

Abstract:  Insulinomas are rare tumors, and approximately 10% of insulinomas are malignant. Accumulating evidence has implicated that we still lack effective therapy to treat the patients who are diagnosed with rare malignant insulinoma. Previous studies have reported that Andrographolide (Andro) could inhibit cell cycle progression, reduce cell invasion and induce cell apoptosis in many common cancer cells. However, the effects of andro are cell type-dependent. So we emplored the Œ≤-TC-6 cells and the RIP1-Tag2 transgenic mouse model of endogenously growing insulinoma model to elucidate the possible anti-cancer effect of Andro on insulinoma, an uncommon type of malignant cancers in this study. Our experiments revealed that Andro significantly inhibited tumor growth at both the early-stage and the advanced-stage of insulinoma through targeting the TLR4/NF-Œ∫B signaling pathway. This work initially provides the evidence that the TLR4/NF-Œ∫B signaling pathway might be vital as a potential therapeutic target, and also indispensable in Andro-mediated anti-cancer effect in insulinoma. 

Retracted: No

PubPeer comments:
 Figure 5B appears to include two images which overlap, although one appears to have been horizontally flipped relative to the other and resized slightly. ***  , 
 Thank you for your comments. I didn t find the mistake before your comment due to I mislabeling the storage photos while taking photos. All the authors checked the original data of this paper carefully and found that we attached the wrong IHC figures of figure 5B. We only photographed 100u00d7 figures while published this paper and the IHC slid were faded and could not be photographed any more. In order to prove the results of this paper, we redone the IHC staining of TLR4 and MyD88 using the previously embedded tumor tissues and found that the results were in accordance with the published results. We send the original 100u00d7 figures and new 20u00d7, 40u00d7 and 100u00d7 figures of figure 5B to the chief editor of IJBS and wish IJBS could give us the opportunity to correct our mistake. It is important to state that this correction do not affect our studyu2019s results in the published paper. The editor replied for me and told me that IJBS will give us decision later. Thank you for pointing out my serious mistakes.  , 
 #2 Thank you for your reply. , 
 Could the authors please also check Figure 4B? Two panels depicting different carcinoma stages appear to show an overlap (marked with yellow boxes).  , 
 There also appears to be an image overlap between Figure 2D (top) and 5B (bottom), after 180-degree rotation, resizing and recoloring. TAM. ***  , 
 Retraction, October 2021: https: www.ijbs.com v17p4092.htm  This article (Andrographolide Suppress Tumor Growth by Inhibiting TLR4 NF-u03baB Signaling Activation in Insulinoma. Qian-Qian Zhang, Yi Ding, Yan Lei, et al. Int J Biol Sci 2014; 10(4): 404-414) has been retracted due to concerns on multiple image duplications as identified by PubPeer users. This raises concerns about the integrity of the data presented in the paper. , 
 #4 Thank you for your comments. All the authors checked the original data of this paper carefully when Actinopolyspora biskrensis indicated the IHC mistakes of TLR4 in the figure 5B on November 2019, and we also found the mistakes you indicated in figure 4B and contacted the chief editor of IJBS to explain the reason that make of the mistakes and uploaded the original data and wish IJBS could give us the opportunity to correct our mistake. It is important to state that this correction do not affect our studyu2019s results in the published paper. The IJBS has accepted the correction of errors and erratum has published on Int J Biol Sci.2020 Jun 25; 16(13):2379-2381. doi: 10.7150 ijbs.49433. eCollection 2020. , 
 #5 Thank you for your comments. Before you indicated this mistake, all the authors checked the original data of this paper carefully when you indicated the IHC mistakes of TLR4 in the figure 5B on November 2019, and we also found the mistakes you indicated in figure 2B and figure 5B, and contacted the chief editor of IJBS to explain the reason that make of the mistakes and uploaded the original data at the same time and wish IJBS could give us the opportunity to correct our mistake. It is important to state that this correction do not affect our studyu2019s results in the published paper. The IJBS has accepted the correction of errors and erratum has published on Int J Biol Sci.2020 Jun 25; 16(13):2379-2381. doi: 10.7150 ijbs.49433. eCollection 2020. However, we did not receive any message about this paper from the International Journal of Biological Sciences or pubpeer through email, phone, or fax. Therefore, we could not respond to the doubt about the content of the mistake when you required. , 
 #6 We confirmed that we did not receive any message about this paper from the International Journal of Biological Sciences or pubpeer through email, phone, or fax recently. Therefore, we could not respond to the doubt about the content of figure 4B, figure 2 and 5B when the journal and pubpeer required. However, all the authors do not agree with the retraction decision of IJBS. Although we have no chance to respond Journalu2019s query, we have uploaded the original data of these mistakes on May 2020 and corrected all these questions in the published Erratum before pubpeer indicated. More importantly, it is indicated IJBS has accepted the correction of errors that erratum published. However, it is inappropriate to question the content of the article and retract the paper based on the questions that we have corrected. , 
 #9 Iu2019m sorry you did not receive a notification from PubPeer. When it works properly, those emails are automatically sent and users donu2019t have any control. It seems that the email address is correct as you received the message in 2019. Iu2019m afraid I cannot give you any advice about contacting the journal. ,