The inhibitory effect of doxycycline on cisplatin-sensitive and -resistant epithelial ovarian cancer
Authors: Wei Wu
Ming-Juan Xu
Bei Ma
Li-Hua Yu
Journal: PloS one (2014)
Discipline: Multidisciplinary
Keywords: anticancer drug; doxycycline; tumorigenesis; epithelial ovarian cancer cells; proliferation
Affiliations: Department of Gynecology and Obstetrics, Changhai Hospital, Second Military Medical University, Shanghai, P.R.China; Department of Physiology, Second Military Medical University, Shanghai, P.R.China., Department of Physiology, Second Military Medical University, Shanghai, P.R.China., Department of Gynecology and Obstetrics, Changhai Hospital, Second Military Medical University, Shanghai, P.R.China.

Abstract:  Background: Detecting a new effective and hypotoxic anticancer drug is an emerging new strategy for cancer chemotherapy. Doxycycline (DC) is a kind of antibiotics but also inhibits tumorigenesis. Methods: MTT and cell invasion assay, flow cytometry, western-blot analysis and nude mice were used to investigate the effects and underlying mechanisms of doxycycline on epithelial ovarian cancer cells. Results: Doxycycline inhibited the proliferation and invasion of SKOV3 and SKOV3/DDP; induced moderate apoptosis of SKOV3/DDP. CXCR4 expression at both mRNA and protein levels was downregulated in both cell lines when treated with doxycycline. Akt and ERK1/2 were involved in doxycycline effect on cell proliferation of SKOV3 but not of SKOV3/DDP. Akt and EKR1/2 phosphorylation were activated by SDF-1α, which was then inhibited by doxycycline in SKOV3. Pro-caspase-3 expression was significantly higher in SKOV3 than that in SKOV3/DDP which was upregulated when treated with doxycycline. In vivo, doxycycline inhibited peritoneal tumor xenograft and decreased malignant ascites. Conclusion: Doxycycline not only has an inhibitory effect on ovarian cancer, but also can increase sensitivity to cisplatin. SDF-1α/CXCR4-regulated Akt and ERK 1/2 activations are probably involved in the antitumor effect of doxycycline on SKOV3 cells, while upregulation of pro-caspase-3 may be the main mechanism involved in SKOV3/DDP cells. 

Retracted: Yes

PubPeer comments:
 2020 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0231890 After this article [1] was published, concerns were raised about results reported in Figs 2, 5 and 6. Specifically: In Fig 2D, the lower portion of panel a appears similar to the upper portion of panel b. The authors reviewed the original data for this experiment and confirmed that the images in these panels were taken from the same culture plate. The ERK panels appear similar in Fig 5B and 5D, and in Fig 5F and 5H. In each case, the similar panels represent different experiments. Lanes 5, 6 of the Akt panel in Fig 5G appear similar to lanes 1, 2 of the p-Akt panel in Fig 6A, when the aspect ratio is adjusted. The p-ERK panels appear similar in lanes 1, 2 of Figs 5D and 6B, when the aspect ratio is adjusted. The u03b2-actin panels for Figs 5A, 5C, 5E, 5G, 6A and 6C appear to be duplicated in Figs 5B, 5D, 5F, 5H, 6B and 6D, respectively. The similar u03b2-actin panels represent the same experimental conditions for each pair. The authors confirmed that for each experiment the same transfer membrane was used to obtain the corresponding p-Akt, Akt, p-ERK, and ERK data, and so the same u03b2-actin data applied. The authors noted that the original data are no longer available for the panels mentioned in the second, third, and fourth bullet points, and so these issues could not be clarified. The figure concerns outlined above also have potential implications for the reliability of quantitative data reported in Figs 2D, 5 and 6. In light of the unresolved image issues and concerns about the reliability of the reported results, the authors and the PLOS ONE Editors retract the article. The authors apologize for the issues with this article. Reference 1.Wu W, Yu L-h, Ma B, Xu M-j (2014) The Inhibitory Effect of Doxycycline on Cisplatin-Sensitive and -Resistant Epithelial Ovarian Cancer. PLoS ONE 9(3): e89841. https: doi.org 10.1371 journal.pone.0089841 pmid:24598933 , 
 Here are the original concerns about the paper, as reported to the journal in April 2014 (6 years before the retraction). Figure 2D. *the lower portion of panel a appears similar to the upper portion of panel b.* ![file] Figure 5B D F H: *The ERK panels appear similar in Fig 5B and 5D, and in Fig 5F and 5H* ![file] Figure 5D 5G 6A 6B: Lanes 5, 6 of the Akt panel in Fig 5G appear similar to lanes 1, 2 of the p-Akt panel in Fig 6A, when the aspect ratio is adjusted. The p-ERK panels appear similar in lanes 1, 2 of Figs 5D and 6B, when the aspect ratio is adjusted.* ![file] ,