Xiao-Ai-Ping Injection Enhances Effect of Paclitaxel to Suppress Breast Cancer Proliferation and Metastasis via Activating Transcription Factor 3
Authors: Yawei Ding
Xiangqi Zhang
Xiao Xiao
Wei Zhang
Junjun Chen
Jiao Yang
Ying Liu
Meizhi Shi
Yonglong Han
Journal: Integrative Cancer Therapies (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Xiao-Ai-Ping injection; activating transcription factor 3; breast cancer; herbal medicine; paclitaxel.
Affiliations: Shanghai Jiao Tong University Affiliated to Sixth People's Hospital, Shanghai, PR China., Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, PR China., Shanghai Ocean University, Shanghai, PR China.

Abstract:  Chemotherapy is an effective treatment for invasive breast cancer. Paradoxically, many recently published findings showed that the first-line chemotherapeutic agent paclitaxel (PTX) showed pro-metastatic effects in the progress of treating breast cancer. Xiao-Ai-Ping (XAP) injection, composed of a traditional herbal medicine, Marsdenia tenacissimae extract, is known to exert antitumor effects on various cancers. However, there are few experimental studies on breast cancer. The underlying mechanism of the antitumor effect of XAP combined with chemotherapy agents has not been fully understood. In the present study, we sought to find the antitumor effects of XAP combined with PTX in vitro and in vivo. The data demonstrated that the combination of XAP with PTX resulted in remarkable enhancement of the pro-apoptotic, migration-inhibiting, and anti-invasive effects of PTX in vitro. Significantly, further study showed the overexpression of ATF3 in PTX-treated cell, while XAP counteracted the change of ATF3 induced by PTX. Moreover, it showed that combination treatment could promote the inhibition of tumor growth in MDA-MB-231 cell xenograft mouse model. Compared with PTX treatment, the downregulation of ATF3 indicated that ATF3 played a pivotal role in the combination of XAP with PTX to exert a synergistic effect. Overall, it is expected that PTX combined with XAP may serve as an effective agent for antitumor treatment, and dampening ATF3 maybe a potential strategy to improve the efficacy of PTX. 

Retracted: No

PubPeer comments:
 Figure 3C appears to have two images which overlap, but which are described differently. Undoubtedly the authors will find that they selected the wrong image during figure assembly. *** ![file] , 
 #1 Dear Editor: Thank you very much for giving us the opportunity to correct the published manuscript entitled  Xiao-Ai-Ping Injection Enhances Effect of Paclitaxel to Suppress Breast Cancer Proliferation and Metastasis via Activating Transcription Factor 3 . We sincerely apologize for any inconvenience caused by the mistake of selecting the wrong image during figure assembly in Figure 3C. The Figure 3C showed the result of Matrigel-coated Transwell invasion assay. Cells in this experiment were divided into 6 groups (Control, XAP 40 mg mL, XAP 80 mg mL, PTX 10 nmol L, XAP 40 mg mL+PTX 10 nmol L, XAP 80 mg mL+PTX 10 nmol L). The experiment was performed 3 times. Images from different views were captured in each group. One of the images in each group was selected as a part of the region in Figure 3C. The original images captured is shown as follows: ![file] The correct image of the XAP 80 mg mL+PTX 10 nmol L group in Figure 3C has been reselected as follows: ![file] We have confirmed that the unintentional mistake does not affect the scientific conclusion of the work in this paper. Once again, great thanks to you for your instructive suggestion to make the data more reliable. If any question arises, please contact me at the email address below, and we will try our best to improve the article. With best wishes, Yours sincerely, Yong-long Han, Ph.D. Corresponding author E-mail: yonglongh@126.com , 
 #2 Thank you for responding. If I understand the authorsu2019 reply, the grid of images above represents the original data. If this understanding is correct, then I am afraid that the problems are much more extensive than the single item shown in #1. The raw data is filled with overlapping and repeated images, some of which I have indicated with the colored boxes below (I got tired of this effort). The original data seems irredeemably flawed. I strongly recommend making the journal aware of this discussion to see what they recommend. *** Enhanced contrast and color ![file] , 
 I should begin by thanking the authors for throwing open their entire archive of images, including all the panels not used in the final assembled Figure. This is a whole new level of transparency. ![file] The overlaps between images within a single row are understandable: within each third of the main grid, a row of 3 or 4 panels contains enlarged details of the Matrigel filter from that experimental repetition - sometimes at different scale. But as well as the three panels of XAP 40 mg mL overlapping with one another, they also overlap with the central panel of Control (requiring a color-clashing mesh of colored rectangles). Even though only one panel from each row appears in the final assembled illustration, this does point to a lapse in how images were archived. , 
 No sign of a correction on the journal website. I will alert them and the funding agency. Funding. The author(s) disclosed receipt of the following financial support for the research, authorship, and or publication of this article: This study was supported by the National Natural Science Foundation of China (81773949), the Research Program of Shanghai Health and Family Planning Commission (20174Y0023, 2018YP003), the Science and Technology Project of Shanghai Pudong New Area Health and Family Planning (PW2017E-2), the Science and Technology Development Fund of Shanghai Pudong New Area (PKJ2017-Y07), and the Hundred Teachers ,