β-hydroxyisovaleryl-shikonin induces human cervical cancer cell apoptosis via PI3K/AKT/mTOR signaling
Authors: Siquan Zhang
Shu Pan
Jing Qian
Dan Lu
Wei Li
Qianqian Feng
Journal: Oncology Letters (2015)
Discipline: CLINICAL MEDICINE
Keywords: HeLa cells; apoptosis; cervical cancer; phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway; β-hydroxyisovaleryl shikonin.

Abstract:  The present study aimed to investigate the inhibitory ability of β-hydroxyisovaleryl-shikonin (β-HIVS) on the proliferation of human cervical cancer HeLa cells and to identify the mechanism of this effect. The HeLa cells were treated with β-HIVS and the inhibition of cell growth was detected by an MTT assay. Flow cytometry was performed to analyze the apoptosis rate and cell cycle distribution of HeLa cells. Reverse transcription-polymerase chain reaction and western blot analysis were used to examine the expression of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway proteins. The results revealed that β-HIVS inhibited HeLa cell proliferation in a dose- and time-dependent manner. With the administration of increasing concentrations of β-HIVS, the apoptotic rate of HeLa cells was also increased. The cell cycle was slightly arrested at the S phase, with ~6% of cells in this phase, subsequent to treatment with 10 µM β-HIVS. In addition, β-HIVS markedly reduced the expression levels of PI3K, AKT, mTOR and 70-kDa ribosomal protein S6 kinase in HeLa cells. β-HIVS promoted cervical cancer cell apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway and suppressing downstream gene expression. The present study is expected to lead to the development of molecular targeted therapy for this signaling pathway as a novel method of cervical cancer treatment. 

Retracted: No

PubPeer comments:
 This paper was found during a systematic search of papers in this journal with possible duplicated images. Fifteen papers in this journal (n=98 examined) were found to contain inappropriately duplicated images. These papers have all been reported to the journal publisher in 2017. The editors promised to  investigate promptly but no action has been taken as of today. Figure 2. Panels B and C look remarkably similar. ![file] , 
 Response to Spandidos Publications for OL-6015-E133963 Dear editor, I am sorry that we made a mistake, which caused a trouble to your Journal.This mistake arose during the uploading process. We re-examined our original data,and found the Panels b was repeatedly uploaded for Panels c in Figure 2. So the Panels c in this published paper is incorrect. The original Panels c in Figure 2 is as follows. Now, I send these original pictures back to you, which hope you verify, and may be able to publish a Corrigendum to accompany our paper. I would like to express my great appreciation to you. If you have any questions about this paper, please contact me in any time. Please check the attached files. Sincerely yours, Dan Lu ![file] ![file] , 
 Response to Spandidos Publications for OL-6015-E133963 Dear editor, I am sorry that we made a mistake, which caused a trouble to your Journal.This mistake arose during the uploading process. We re-examined our original data,and found the Panels b was repeatedly uploaded for Panels c in Figure 2. So the Panels c in this published paper is incorrect. The original Panels c in Figure 2 is as follows. Now, I send these original pictures back to you, which hope you verify, and may be able to publish a Corrigendum to accompany our paper. I would like to express my great appreciation to you. If you have any questions about this paper, please contact me in any time. Please check the attached files. Sincerely yours, Dan Lu ![file] ![file] , 
 Corrigendum [8 January 2021] . --------------------------------------------------- Subsequently to the publication of the above paper, an interested reader drew to the authorsu2019 attention that, on p. 3437, the data shown in Fig. 2B and C were strikingly similar. The authors have re-examined their data, and realized that the data correctly shown for Fig. 2B was reused in Fig. 2C. However, the authors were able to locate the original data pertaining to Fig. 2C, and the corrected version of Fig. 2 is shown opposite. The authors regret the error that was made in the preparation of the published figure, and confirm that this error did not affect the conclusions reported in the study. The authors are grateful to the editor of Oncology Letters for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologize to the readership for any inconvenience caused. , 
 Thank you for the update, Hoya. I was the  interested reader and reported this concern to the journal publisher (Spandidos) in September 2017. However, I was not notified about this correction. ,