[Corrigendum] Endophytic fungi from mangrove inhibit lung cancer cell growth and angiogenesis in vitro.

Subsequently to the publication of the above article, the authors have drawn to the attention of the Editorial Office that a few inadvertent errors were made during the assembly of Fig. 6 on p. 1802. In the first instance, the images selected to represent the A549 cell line in Fig. 6A were inadvertently shown as the data for the NCI­H460 cell line in Fig. 6C and vice versa, and so the data shown for Fig. 6A and C have been interchanged in the revised version of this figure. Moreover, the representative image for panel '3' in Fig. 6A of the above article (and so, now panel '3' in Fig. 6C of the corrected version) was wrongly copied across from that of panel '2' in Fig. 6C (now, panel '2' in Fig. 6A of the corrected version). The authors were able to re­examine their original data files, and realize how the errors were made during the assembly of this figure. The revised version of Fig. 6, with the data originally shown in Fig. 6A and C now interchanged, also showing the correct data for panel '3' in Fig. 6C, is shown on the next page. Note that the errors made in assembling this figure did not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and all the authors agree with its publication. They also apologize to the readership for any inconvenience caused. [Oncology Reports 37: 1793­1803, 2017; DOI: 10.3892/or.2017.5366].

[Corrigendum] Epigallocatechin­3­gallate inhibits nicotine­induced migration and invasion by the suppression of angiogenesis and epithelial­mesenchymal transition in non­small cell lung cancer cells.

Subsequently to the publication of the above paper, the authors have drawn to the attention of the Editorial Office that a pair of the data panels showing the results of wound­healing assay experiments (in Fig. 1A) and Transwell invasion assays (in Fig. 1B) on p. 2975 were inadvertently featured incorrectly in this figure. Specifically, in Fig. 1A, the 'nicotine + 25 µM EGCG / 0 h' data panel was erroneously copied across to represent the 'nicotine + 0 µM EGCG / 0 h' image, whereas in Fig. 1B, the representative invasion image for the 'nicotine + 10  µM  EGCG' experiment was also incorrectly placed. The authors were able to re­examine their original data files, and realize how the errors were made during the assembly of this figure. The revised version of Fig. 1, showing the correct data for the 'nicotine + 0 µM EGCG / 0 h' in Fig. 1A and the 'nicotine + 10  µM  EGCG' experiment in Fig. 1B, is shown on the next page. Note that the errors made in assembling this figure did not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and all the authors agree with its publication. They also apologize to the readership for any inconvenience caused. [Oncology Reports 33: 2972­2980, 2015; DOI: 10.3892/or.2015.3889].

Overexpression of Human Papillomavirus Type 16 Oncoproteins Enhances Epithelial-Mesenchymal Transition via STAT3 Signaling Pathway in Non-Small Cell Lung Cancer Cells.

The human papillomavirus (HPV) infection may be associated with the development and progression of non-small cell lung cancer (NSCLC). However, the role of HPV-16 oncoproteins in the development and progression of NSCLC is not completely clear. Epithelial-mesenchymal transition (EMT), a crucial step for invasion and metastasis, plays a key role in the development and progression of NSCLC. Here we explored the effect of HPV-16 oncoproteins on EMT and the underlying mechanisms. NSCLC cell lines, A549 and NCI-H460, were transiently transfected with the EGFP-N1-HPV-16 E6 or E7 plasmid. Real-time PCR and Western blot analysis were performed to analyze the expression of EMT markers. A protein microarray was used to screen the involved signaling pathway. Our results showed that overexpression of HPV-16 E6 and E7 oncoproteins in NSCLC cells significantly promoted EMT-like morphologic changes, downregulated the mRNA and protein levels of EMT epithelial markers (E-cadherin and ZO-1), and upregulated the mRNA and protein levels of EMT mesenchymal markers (N-cadherin and vimentin) and transcription factors (ZEB-1 and Snail-1). Furthermore, the HPV-16 E6 oncoprotein promoted STAT3 activation. Moreover, WP1066, a specific signal transducer and activator of transcription 3 (STAT3) inhibitor, reversed the effect of HPV-16 E6 on the expression of ZO-1, vimentin, and ZEB-1 in transfected NSCLC cells. Taken together, our results suggest that overexpression of HPV-16 E6 and E7 oncoproteins enhances EMT, and the STAT3 signaling pathway may be involved in HPV-16 E6-induced EMT in NSCLC cells.

Endophytic fungi from mangrove inhibit lung cancer cell growth and angiogenesis in vitro.

The secondary metabolites of mangrove-derived endophytic fungi contain multiple substances with novel structures and biological activities. In the present study, three types of mangrove plants, namely Kandelia candel, Rhizophora stylosa and Rhizophoraceae from Zhanjiang region including the leaves, roots and stems were collected, and endophytic fungi were isolated, purified and identified from these mangrove plants. MTT assay was used to observe the effects of the isolated endophytic fungi on the growth of A549 and NCI-H460 lung cancer cells. The effect of the endophytic fungi on lung cancer angiogenesis in vitro induced by the HPV-16 E7 oncoprotein was observed. Our results showed that 28 strains of endophytic fungi were isolated, purified and identified from the three types of mangrove plants. Ten strains of endophytic fungi significantly suppressed the growth of A549 and NCI-H460 cells. The average inhibitory rates in the A549 cells were 64.4, 59.5, 81.9, 43.9, 58.3, 56.2, 48.3, 42.4, 93.0 and 49.7%, respectively. The average inhibitory rates in the NCI-H460 cells were 41.2, 49.3, 82.7, 40.7, 53.9, 52.6, 56.8, 64.3, 91.0 and 45.6%, respectively. Particularly, three strains of endophytic fungi markedly inhibited HPV-16 E7 oncoprotein­induced lung cancer angiogenesis in vitro. These findings contribute to the further screening of potential chemotherapeutic agents from mangrove-derived endophytic fungi.

ERK Signaling Pathway Is Involved in HPV-16 E6 but not E7 Oncoprotein-Induced HIF-1α Protein Accumulation in NSCLC Cells.

Extracellular signal-regulated kinase (ERK)1/2 signaling pathway plays a critical role in regulating tumor angiogenesis. Our previous studies have demonstrated that HPV-16 oncoproteins enhanced hypoxia-inducible factor-1α (HIF-1α) protein accumulation and vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) expression in non-small cell lung cancer (NSCLC) cells, thus contributing to angiogenesis. In this study, we further investigated the role of ERK1/2 signaling pathway in HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in NSCLC cells. Our results showed that HPV-16 E6 and HPV-16 E7 oncoproteins promoted the activation of ERK1/2 signaling pathway in A549 and NCI-H460 cells. Moreover, PD98059, a specific inhibitor of ERK1/2, blocked in vitro angiogenesis stimulated by HPV-16 E6 but not E7 oncoprotein. Additionally, HIF-1α protein accumulation and VEGF and IL-8 expression in NSCLC cells induced by HPV-16 E6 but not E7 oncoprotein were significantly inhibited by PD98059. Taken together, our results suggest that ERK1/2 signaling pathway is involved in HPV-16 E6 but not E7 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression in NSCLC cells, leading to the enhanced angiogenesis in vitro.

Epigallocatechin-3-gallate inhibits nicotine-induced migration and invasion by the suppression of angiogenesis and epithelial-mesenchymal transition in non-small cell lung cancer cells.

Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea extract, has been found to have anticancer activities in various types of cancer. However, the underlying mechanisms are not completely clear. In the present study, the effects of EGCG on migration, invasion, angiogenesis and epithelial-mesenchymal transition (EMT) induced by nicotine in A549 non-small cell lung cancer (NSCLC) cells were investigated, and the underlying molecular mechanisms were preliminarily examined. The results showed that different concentrations of EGCG significantly inhibited nicotine-induced migration and invasion. Moreover, EGCG reversed the upregulation of HIF-1α, vascular endothelial growth factor (VEGF), COX-2, p-Akt, p-ERK and vimentin protein levels and the downregulation of p53 and ß-catenin protein levels mediated by nicotine in A549 cells, but had no significant effect on their mRNA levels. Furthermore, EGCG markedly inhibited HIF-1α-dependent angiogenesis induced by nicotine in vitro and in vivo, and suppressed HIF-1α and VEGF protein expression induced by nicotine in A549 xenografts of nude mice. Taken together, the results indicated that EGCG inhibited nicotine-induced angiogenesis and EMT, leading to migration and invasion in A549 cells. The results of the present study suggested that EGCG can be developed into a potential agent for the prevention and treatment of smoking-associated NSCLC.