[Retracted] Exosome­mediated transfer of lncRNA RP11­838N2.4 promotes erlotinib resistance in non­small cell lung cancer.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that various panels showing the cellular data in Fig. 1B, the western blotting data shown in Figs. 2B and 3C, the TEM scanning data shown in Fig. 4B, the ChIP assay data in Fig. 2F and the flow cytometric assay data in Fig. 3D were strikingly similar to data appearing in different form in other articles by different authors from different research institutions. Owing to the fact that the contentious data in the above article had already been published, or were already under consideration for publication elsewhere, prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors independently contacted the Editorial Office to request the retraction of this paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 53: 527­538, 2018; DOI: 10.3892/ijo.2018.4412].

Atractylodin induces oxidative stress-mediated apoptosis and autophagy in human breast cancer MCF-7 cells through inhibition of the P13K/Akt/mTOR pathway.

This study aimed to determine the apoptosis and autophagy-inducing mechanism of atractylodin in human breast cancer MCF-7 cells. The molecular mechanism of anticancer activity of atractylodin was confirmed by assessing the levels of reactive oxygen species (ROS) level, lipid peroxidation (LPO), antioxidants activity, dual staining, and comet assay. Moreover, cleaved caspases 3, 8, and 9, and signaling proteins, such as p53, Bcl-2, and Bax, phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin(P13K/Akt/mTOR), LC3I and LC3II, and beclin-1 were analyzed. In MCF-7 cells treated with atractylodin, the concentration-dependent toxicity, increased LPO, increased production of ROS, and decreased activity of superoxide dismutase, catalase, and glutathione peroxidasewere observed. In MCF-7 cells, atractylodin administration decreased Bcl-2 expression while activating the expression of p53, Bax, cleaved caspase-3, caspase-8, and caspase-9 apoptotic members. Furthermore, atractylodin blocked the P13K/Akt/mTOR signaling pathway, increased the conversion of LC3I to its lipidated form of LC3II, and increased beclin-1 expression, whereas downregulated the p62 expression in MCF-7 cells. As a result, altering apoptotic and autophagy-related biomarkers, atractylodin triggered apoptosis and autophagy in MCF-7 cells. As a result, atractylodin could be utilized to treat human breast cancer after the proper clinical trial.

Exosome-mediated transfer of lncRNA RP11­838N2.4 promotes erlotinib resistance in non-small cell lung cancer.

Currently, resistance to tyrosine kinase inhibitors, such as erlotinib, has become a major obstacle for improving the clinical outcome of patients with metastatic and advanced­stage non-small cell lung cancer (NSCLC). While cell behavior can be modulated by long non-coding RNAs (lncRNAs), the roles of lncRNAs within extracellular vesicles (exosomes) are largely unknown. To this end, in this study, the involvement and regulatory functions of potential lncRNAs wrapped by exosomes during the development of chemoresistance in human NSCLC were investigated. Erlotinib-resistant cell lines were established by grafting HCC827 and HCC4006 cells into mice and which were treated with erlotinib. After one treatment course, xenografted NSCLC cells were isolated and transplanted into nude mice again followed by erlotinib treatment. This process was repeated until 4th generation xenografts were isolated and confirmed to be erlotinib-resistant NSCLC cells. lncRNA microarray assays followed by RT­qPCR were then performed which identified that lncRNA RP11­838N2.4 was upregulated in erlotinib-resistant cells when compared to normal NSCLC cells. Furthermore, bioinformatics analysis and chromatin immunoprecipitation revealed that forkhead box protein O1 (FOXO1) could bind to the promoter region of lncRNA RP11­838N2.4, resulting in its silencing through the recruitment of histone deacetylase. Functional experiments demonstrated that the knockdown of lncRNA RP11­838N2.4 potently promoted erlotinib-induced cytotoxicity. Furthermore, extracellular lncRNA RP11­838N2.4 could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating erlotinib resistance. Treatment-sensitive cells with exosomes containing lncRNA RP11­838N2.4 induced erlotinib resistance, while the knockdown of lncRNA RP11­838N2.4 abrogated this effect. In addition, the serum expression levels of exosomal lncRNA RP11­838N2.4 were upregulated in patients exhibiting resistance to erlotinib treatment. On the whole, exosomal lncRNA RP11­838N2.4 may serve as a therapeutic target for patients with NSCLC.