Amarogentin secoiridoid inhibits in vivo cancer cell growth in xenograft mice model and induces apoptosis in human gastric cancer cells (SNU-16) through the mediation of G2/M cell cycle arrest and PI3K/Akt signalling pathway.

The Editors of JBUON issue an Expression of Concern to 'Amarogentin secoiridoid inhibits in vivo cancer cell growth in xenograft mice model and induces apoptosis in human gastric cancer cells (SNU-16) through G2/M cell cycle arrest and PI3K/Akt signalling pathway', by Jian-Guo Zhao, Ling Zhang, Xiao-Jun Xiang, Feng Yu, Wan-li Ye, Dong-Ping Wu, Jian-Fang Wang, Jian-Ping Xiong, JBUON 2016;21(3):609-617; PMID:27569081. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

HHIP overexpression inhibits the proliferation, migration and invasion of non-small cell lung cancer.

OBJECTIVE: The primary purpose of this study is to investigate the effect of hedgehog-interacting protein (HHIP) overexpression on the proliferation, migration and invasion of non-small cell lung cancer (NSCLC). METHODS: Firstly, HHIP gene expression data of NSCLC tissues and normal tissues were obtained from GSE18842/GSE19804/GSE43458 databases of the Gene Expression Omnibus (GEO) database and then validated by TCGA NSCLC database in a cohort of 1027 cases of NSCLC patients and 108 cases of normal people. A chi-square test was used to analyze the relationship between HHIP expression and clinicopathological characteristics of NSCLC. The expression levels of HHIP in NSCLC cells were detected by quantitative-real time PCR. The function of HHIP was investigated by a series of in vitro assays. CCK-8, wounding healing, Transwell invasion assay were utilized to explore the mechanisms of HHIP. RESULTS: HHIP mRNA were significantly down-regulated in NSCLC in three GEO databases and TCGA database (P<0.05). This result was confirmed in NSCLC cell lines by qRT-PCR analysis, its expression in normal NSCLC cell line BEAS-2B was significantly higher than that in NSCLC cells. Chi-square test results showed that the low expression of HHIP was correlated with gender, cancer type, TNM stage and tumor size. Functional experimental results showed that over-expressing HHIP significantly decreased the ability of cell proliferation, migration and invasion in NSCLC cells (P<0.05). CONCLUSION: Overall, the above results indicated that HHIP could regulate proliferation, migration and invasion, and could be used as a judging criterion for identifying NSCLC classification and stage.

Erratum: Amarogentin secoiridoid inhibits in vivo cancer cell growth in xenograft mice model and induces apoptosis in human gastric cancer cells (SNU-16) through G2/M cell cycle arrest and PI3K/Akt signalling pathway.

In the version of this article initially published, in Volume 21, issue 3, the first affiliation (affiliation number 1) was incorrectly stated as "Department of Pathology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey". The correct affiliation is "Department of Oncology, Shaoxing People's Hospital ,Shaoxing Hospital of Zhejiang University, Shaoxing 312000,China'. This error appeared only in the PubMed database and not in the print form of the Journal.

Amarogentin secoiridoid inhibits in vivo cancer cell growth in xenograft mice model and induces apoptosis in human gastric cancer cells (SNU-16) through G2/M cell cycle arrest and PI3K/Akt signalling pathway.

PURPOSE: To investigate the in vitro and in vivo antitumor effects of amarogentin in SNU-16 human gastric cancer cells as well as in nude mice xenograft model. The effects of this compound on cell apoptosis, cell cycle phase distribution and PI3K/Akt and m-TOR signalling pathways were also studied in detail. METHODS: MTT assay was used to study the effect of amarogentin on SNU-16 cell viability while clonogenic assay indicated the effect of the compound on colony formation tendency of these cells. Phase contrast microscopy revealed the effect on cellular morphology while flow cytometry was engaged to study the effects on cell apoptosis and cell cycle arrest. SNU-16 cancer cells were subcutaneously inoculated into nude mice to investigate the in vivo antitumor effects of amarogentin. RESULTS: Amarogentin induced potent, dose-dependent as well as time-dependent cytotoxic effects on the growth of SNU-16 human gastric cancer cells. Amarogentin also inhibited the colony forming capability of these tumor cells and its treatment led to morphological alterations in these cells in which the cells became withered and rounded, detached from one another and adopted irregular shapes while floating freely in the culture medium. In comparison to untreated control cells, the amarogentin treated cells with 10, 50 and 75 µM exhibited 32.5, 45.2 and 57.1 % apoptotic cells, respectively. Amarogentin induced potent and dose-dependent G2/M cell cycle arrest in these cells and led to downregulation of m-TOR, p-PI3K, PI3K, p-Akt and Akt and upregulation of cyclin D1 and cyclin E protein expressions. The tumor tissues obtained from the amarogentin-treated mice were much smaller than the tumor tissues derived from the control group. CONCLUSION: Amarogentin exerts potent in vitro and in vivo antitumor effects in SNU-16 cell model as well as in nude mice xenograft model. These antitumor effects were found to be mediated through apoptosis induction, G2/M cell cycle arrest and downregulation of PI3K/Akt/m-TOR signalling pathways.

[Concurrent chemoradiotherapy for locally advanced unresectable extrahepatic cholangiocarcinoma: a report of 19 cases].

OBJECTIVE: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy for patients with locally advanced unresectable extrahepatic cholangiocarcinoma. METHODS: Thirty-eight patients with locally advanced unresectable extrahepatic cholangiocarcinoma admitted in Shaoxing People's Hospital from February 2007 to February 2012 were enrolled in the study. They were randomized into sequential chemoradiotherapy (n=19) or concurrent chemoradiotherapy group (n=19). All patients were treated with intensity modulated radiation therapy (IMRT). Patients in concurrent chemoradiotherapy group received the regimen of gemcitabine plus oxaliplatin. Tumor response and adverse effects were observed periodically. The primary end points were disease progression-free survival (PFS) and overall survival (OS). RESULTS: The response rates of sequential chemoradiotherapy and concurrent chemoradiotherapy groups were 42.1% (8/19) and 63.2% (12/19). The disease control rates of them were 78.9% (15/19) and 84.2% (16/19))， respectively. The median PFS of sequential chemoradiotherapy group and concurrent chemoradiotherapy group was 8.3 (95%CI: 7.6-9.0) and 10.4 months (95%CI: 9.4-11.4, P=0.037), and the median OS in two groups were 14.2 (95%CI: 12.6-15.8) and 15.6 months (95%CI: 14.2-17.0, P=0.095), respectively. The major adverse reactions were controllable hematology toxicity and gastrointestinal reaction. There was no significant difference in incidence of adverse reactions between two groups (P>0.05). CONCLUSION: Sequential chemoradiotherapy and concurrent chemoradiotherapy may improve PFS and OS in patients with locally advanced unresectable extrahepatic cholangiocarcinoma, and both are well-tolerated. In addition, concurrent chemoradiotherapy might provide additional PFS benefit and would be preferable.