Norcantharidin reverses cisplatin resistance and inhibits the epithelial mesenchymal transition of human non‑small lung cancer cells by regulating the YAP pathway
Authors: Yong Gao
Cuijie Shao
Dan Jin
Deqiang Wang
Jiwei Guo
Yan Wu
Journal: Oncology Reports (2018)
Discipline: CLINICAL MEDICINE
Keywords: Non-small cell lung cancer; NSCLC; resistance; Norcantharidin; DDP
Affiliations: Department of Pain Medicine, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China., Cancer Research Institute, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China., Department of Pain Medicine, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China.

Abstract:  Non‑small cell lung cancer (NSCLC) accounts for &gt;80% of all lung cancer cases, which are the leading cause of cancer‑related mortality worldwide. The clinical efficacy of available therapies for NSCLC is often limited due to the development of resistance to anticancer drugs, particularly to cisplatin (DDP). Norcantharidin (NCTD) is a traditional Chinese medicine used in the treatment of many types of cancer, to which patients do not develop resistance. The aim of the present study was to examine the potential synergistic effects of NCTD and DPP on the viability of the the DDP‑resistant NSCLC cell line, A549/DDP. We further explored the potential underlying mechanisms by examining the expression of the oncogene, Yes-associated protein 1 (YAP), whose activation was recently found to be associated with drug resistance. We further examined a series of human lung cancer cell lines and tissues from patients with lung cancer, which revealed that YAP activation contributed to lung cancer initiation, progression and metastasis, and was associated with a poor prognosis, and confering resistance against targeted therapies. Moreover, YAP expression was evaluated in the A549/DDP cells treated with NCTD, DDP, or both drugs. The combined treatment significantly sensitized the A549/DDP cells to DDP‑induced growth inhibition by reducing YAP promoter activity (based on transcriptional expression) and the expression of its target genes, connective tissue growth factor (CTGF) and cysteine rich angiogenic inducer 61 (CYR61). Furthermore, compared to the individual treatments, combined treatment increased cell apoptosis and senescence, and decreased epithelial‑to‑mesenchymal transition and the cell migratory and invasive ability. On the whole, our data indicate that the application of NCTD with reverses DDP resistance and thus, this combined treatment may have promising prospects for use in improving the outcome of patients with NSCLC. 

Retracted: Yes

PubPeer comments:
 Could the authors please comment on the apparent we use of bands in figure 1B? *** Inverse ![file] *** Original ![file] , 
 #1 Same request on Figure 6C. I will refrain from further thoughts until authors have had an opportunity to respond. *** ![file] , 
 Dear Dr Biskrensis: I appreciate your interest in our work and your comment on our article in the article. I have carefully re-examined our manuscript and experimental records. The quality for some WB bands in Figures are low, leading to some confusion about the results. In fact, theses bands are the different bands with difference as indicated in the Figures. Thank you again for reading my article carefully, and I appreciates your work very much agian! ![file] ![file] , 
 #3 Thank you for your reply. Could you please provide the original uncropped scans? As you are probably aware, slight differences can appear even in identical images after image compression and processing. It certainly is possible that I am mistaken, and the original scans will alleviate my concerns. , 
 Thank you for your reply. Here are the original uncropped scans. Figure 6C![file] Figure 1B![file] , 
 #5 Thank you for your reply. I agree there appear to be some differences and I may be mistaken, but the images in the paper appear unexpectedly similar. The images you have provided here do show more differences but they appear to be already cropped, and perhaps printed on paper (?). An image of the uncropped gel from which these came could better address my concerns. I appreciate your patience and cooperation. , 
 Dear Actinopolyspora Biskrensis. when we performed western blot, the PDVF membrane was cut to the indecated size instructed by the protein size and number inorder to incubate with antibdoy, respectively. The images were obtained by the ChemiDoc TMTM XRS+ (Bio-Rad) instead of the developing the film to get the original uncropped scans. , 
 The colony forming assays feature a duplication. ![file] But, wait, there is more. The same assays have been featured in at least two other publications: https: pubpeer.com publications 30C4B226FBDA768041AF53AB1F391A https: pubpeer.com publications B7B7BAA24DEDB2643B70ADECA5DCC9 , 
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