Topical Treatment with Xiaozheng Zhitong Paste (XZP) Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling
Authors: Liping Yang
Xiangying Kong
Yebo Gao
Maobo Du
Baojin Hua
Honggang Zheng
Weidong Li
Wei Hou
Yanju Bao
Journal: Evidence-based Complementary and Alternative Medicine (2015)
Discipline: CLINICAL MEDICINE
Keywords: Xiaozheng Zhitong Paste; bone cancer pain; Wistar rats; prostate cancer; bone structural damage
Affiliations: Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beixiange 5, Xicheng District, Beijing 100053, China., Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beixiange 5, Xicheng District, Beijing 100053, China ; Beijing University of Chinese Medicine, Beijing North Third Ring Road No. 11, Chaoyang District, Beijing 100029, China., Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Nanxiaojie, Dongzhimen District, Beijing 100700, China., Department of Nephrology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beixiange 5, Xicheng District, Beijing 100053, China.

Abstract:  To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP) on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P&lt;0.05). Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were detected in the XZP-treated rats (P&lt;0.05 for all). Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats. 

Retracted: Yes

PubPeer comments:
 Figure 2(b) appears to show a few similar images which share a common source. Two images appear to be different images of the same sample. *** ![file] , 
 Figure 5(a) *** ![file] , 
 Figure 5(b)... and Iu2019m stopping. *** ![file] , 
 Published 21 Dec 2020 Evidence-Based Complementary and Alternative Medicine has retracted the article titled u201cTopical Treatment with Xiaozheng Zhitong Paste (XZP) Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL RANK OPG Signalingu201d [1]. As raised on PubPeer [2], the article was found to contain images with signs of duplication and manipulation in Figures 2 and 5. (i)tThe medium dose panel in Figure 2(b), showing 3D micro-CT images of the tibia, shows high similarity to parts of the Placebo and High-dose panels and may be a composite image: (1)tThe upper part of the Medium dose is similar to the upper part of the Placebo panel. (2)tThe lower part of the Medium-dose panel is similar to the lower part of the High-dose panel. (ii)tFigures 5(a) and 5(b) include repeated images: (1)tIn Figure 5(a), the bottom right of the Control panel is the same as the top left of the Medium-dose panel. (2)tIn Figure 5(b), the top right of the Low-dose panel is the same as the bottom left of the High-dose panel. (iii)tComparing the submitted figures to the published figures: (1)tIn Figure 2(b), the 3D micro-CT images of the tibias are not the same between the submitted, accepted, and published versions of the article and show clear signs of editing. (2)tIn Figure 5(b), the High-dose panel in the submitted version is the same as the Medium-dose panel in the published version, but vertically stretched. (3)tThe High-dose panel in Figure 5(a) in the submitted version is the same as the Low-dose panel in Figure 5(b) in the published version. The authors do not agree with retraction and provided what they said were the correct files for Figures 2(b), 5(a), and 5(b). ,