Oxymatrine Synergistically Potentiates the Antitumor Effects of Cisplatin in Human Gastric Cancer Cells
Authors: Yan Liu
Wei Dai
Wei Liu
Lei Qin
Tingting Bi
Genhai Shen
Quangen Gao
Journal: Journal of Cancer (2018)
Discipline: CLINICAL MEDICINE
Keywords: Cisplatin; Gastric cancer; Oxymatrine; Reactive oxygen species; Synergistically.
Affiliations: Department of General Surgery, Wujiang No.1 People's Hospital affiliated to Nantong University, Suzhou, Jiangsu 215200, PR China., Department of General Surgery, Hepatobiliary surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215200, PR China.

Abstract:  Cisplatin (CDDP) has been extensively used for gastric cancer (GC) treatment but limited by drug resistance and severe toxicity. The chemo-sensitizers that enhance its efficiency and overcome its limitation are urgently needed. Oxymatrine (OMT), a primary active ingredient from the dry roots of Sophora favescens, has shown powerful anti-cancer property with little side-effect. In this study, we explored the chemo-sensitization of OMT to potentiate the anti-tumor effect of CDDP. GC cell lines were dealt with OMT and/or CDDP and then subjected to different experimental methods. We found that OMT could significantly potentiate the CDDP-caused BGC-823 and SGC7901 cells viability loss, and OMT acts synergistically with CDDP. The combinative treatment could arrest cell cycle in G0/G1 phase by increasing p21, p27 and decreasing cyclin D1, and induced apoptosis by ROS generation and AKT/ERK inactivation. Inhibition of ROS respectively reversed the cell death induced by OMT and/or CDDP, suggesting the pivotal roles of ROS in the process. Moreover, OMT enhanced the antitumor effects of CDDP in nude mice bearing BGC823 tumor xenografts in vivo. Taken together, this study highlights that the co-treatment with OMT and CDDP exerted synergistic antitumor effects in GC cells, and that these effects may be mediated by ROS generation and inactivation of the AKT/ERK pathways. 

Retracted: Yes

PubPeer comments:
 Figure 3A appears to have two images which overlap, after rotation and resizing. It appears that the samples are described as having been treated differently. If correct, it is difficult to believe that this could have been only an accidental image selection during figure assembly. *** Original ![file] *** After rotation and resizing ![file] *** Overlay ![file] , 
 Thanks for pointing the mistakes. I take it very seriously. We checked carefully and believed we had made a mistake. During the images preparation, multiple photographs of random fields in two directions per sample were taken, and then cut to the same size (190dpi u00d7 190dpi) in the Photoshop (On Mach 31, 2018). One photograph of OMT treatment group in a different direction was accidentally mis-used in group OMT+CDDP in Figure 3a. Here, we sincerely apologize for our carelessness. We will contact the editor as soon as possible to replace these images. We sincerely appreciate your help to point out the errors.![file] ![file] , 
 *[right]* Figure 7.  Combination of OMT and CDDP arrests tumor growth.... (d) The expression levels of Ki67, **p-AKT, and p-ERK** in xenograft tumors were determined by immunohistochemical analysis . *[left]* Figure 7 from [Liu et al (2016)] .  Oxymatrine upregulation of Bax and caspase 3, and downregulation of Bcl-2 and Ki67 in SMMC-7721 xenografts. A, Hematoxylin and eosin (H E) staining analyses of the pathological features of the tumors from the 4 groups (original magnification, 400u0004). B-E, The expression of **caspase 3, Bax, Bcl-2**, and Ki67 in xenograft tumors was analyzed by immunohistochemistry . *[middle]* rows B and C, rotated through 90 deg, with some panels rotated through 270 deg. 8 pairs of overlapping panels, despite different conditions and IHC targets. ![] , 
 Thank you very much for your comments again. I take it very seriously. We will investigate and look at the original image files to verify if the confusion occurred during these image processing. If so, we will promptly contact the magazine and deal with it. Best wishes , 
 #4 Thank you for responding. I, too, have contacted the journal. , 
 Retracted [20 April 2021] .  Regarding our paper, we recently found that during image preparation, one photograph of OMT treatment group in a different direction was accidentally misused in group OMT+CDDP in Figure 3a. And during the process of preparing Figure 7d, the selections of representative p-AKT and p-ERK images were mistakenly confused with the images from our other experiments. In order to maintain rigorousness and completeness of the article, the corresponding authors decide to withdraw this article and to perform further experiments to verify the data again. After careful consideration by all authors, we believe it is most appropriate to retract the article at this time. We sincerely apologize to readers, editors, and reviewers for our mistakes. Cited five times (not counting this retraction). ,