VSTM2L is a promising therapeutic target and a prognostic soluble-biomarker in cholangiocarcinoma

The aim of the present study is to provide a rational background for silencing the V-set and transmembrane domain containing 2 like (VSTM2L) in consort with recognising soluble VSTM2L against cholangiocarcinoma. A therapeutic target against cholangiocarcinoma was selected using iterative patient partitioning (IPP) calculation, and it was verified by in vitro and in silico analyses. VSTM2L was selected as a potential therapeutic target against cholangiocarcinoma. Silencing the VSTM2L expression significantly attenuated the viability and survival of cholangiocarcinoma cells through blockade of the intracellular signalling pathway. In silico analysis showed that VSTM2L affected the positive regulation of cell growth in cholangiocarcinoma. Liptak's z value revealed that the expression of VSTM2L worsened the prognosis of cholangiocarcinoma patients. In addition, soluble VSTM2L was significantly detected in the whole blood of cholangiocarcinoma patients compared with that of healthy donors. Our report reveals that VSTM2L might be the potential therapeutic target and a soluble prognostic biomarker against cholangiocarcinoma

Soluble TGFBI aggravates the malignancy of cholangiocarcinoma through activation of the ITGB1 dependent PPARγ signalling pathway

BackgroundCholangiocarcinoma is a devastating cancer with a poor prognosis. Previous reports have presented conflicting results on the role of transforming growth factor-β-induced protein (TGFBI) in malignant cancers. Currently, our understanding of the role of TGFBI in cholangiocarcinoma is ambiguous. The aim of the present study was to investigate the role of TGFBI in human cholangiocarcinoma.MethodsIterative patient partitioning (IPP) scoring and consecutive elimination methods were used to select prognostic biomarkers. mRNA and protein expression levels were determined using Gene Expression Omnibus (GEO), Western blot and ELISA analyses. Biological activities of selected biomarkers were examined using both in vitro and in vivo assays. Prognostic values were assessed using Kaplan-Meier and Liptak's z score analyses.ResultsTGFBI was selected as a candidate cholangiocarcinoma biomarker. GEO database analysis revealed significantly higher TGFBI mRNA expression levels in cholangiocarcinoma tissues compared to matched normal tissues. TGFBI protein was specifically detected in a soluble form in vitro and in vivo. TGFBI silencing evoked significant anti-cancer effects in vitro. Soluble TGFBI treatment aggravated the malignancy of cholangiocarcinoma cells both in vitro and in vivo through activation of the integrin beta-1 (ITGB1) dependent PPARγ signalling pathway. High TGFBI expression was associated with a poor prognosis in patients with cholangiocarcinoma.ConclusionsOur data suggest that TGFBI may serve as a promising prognostic biomarker and therapeutic target for cholangiocarcinoma

Methodical selected coptisine attenuates the malignancy of cholangiocarcinoma through the blockade of EGFR signalling

The aim of the present study is to provide a methodical platform for the development of lead compounds against cholangiocarcinoma. Coptisine was selected as a potential anti-cancer nominee from a pool of phytochemicals using an in silico 3-D docking screening technique and validated the anti-cancer effects against cholangiocarcinoma through the blockade of EGFR signaling depending on the cellular degradation. We also verified that coptisine had no cytotoxicity in different human normal cells when compared with the clinically approved anti-cancer drug, erlotinib. In vitro and in silico analyses revealed that coptisine can suppress the expression of various oncogenic molecules and administrating coptisine showed an anti-cholangiocarcinoma tumor growth or recurrence using in vivo models. Collectively, we propose that a well-organized methodical 3-D docking screening platform is an innovative technique for the discovery of anti-cancer drugs against malignant tumors, and coptisine might be a safe and effective anti-cancer reagent against cholangiocarcinoma

Kaempferol Inhibits Pancreatic Cancer Cell Growth and Migration through the Blockade of EGFR-Related Pathway <i>In Vitro</i>

<div><p>Pancreatic cancer is one of the most appalling cancers with a pessimistic prognosis. Despite many therapies, there has been no improvement of survival rates. In this study, we assessed the anti-cancer effects of kaempferol, a well known flavonoid having functional bio-activity against various malignant tumors. Kaempferol had anti-cancer effects on Miapaca-2, Panc-1, and SNU-213 human pancreatic cancer cells. In a dose-dependent manner, kaempferol decreased viability of these pancreatic cancer cells by increasing apoptosis. In particular, kaempferol effectively inhibited the migratory activity of human pancreatic cancer cells at relatively low dosages without any toxicity. The anti-cancer effect of kaempferol was mediated by inhibition of EGFR related Src, ERK1/2, and AKT pathways. These results collectively indicate that kaempferol, a phytochemical ingredient reported to have anti-viability and anti-oxidant properties, can act as a safety anti-migration reagent in human pancreatic cancer cells, which provide the rationale for further investigation of kaempferol as a strong candidate for the potential clinical trial of malignant pancreatic cancers.</p></div

The effects of different doses of kaempferol on viability of human pancreatic cancer cells.

<p>(A-C) Miapaca-2, Panc-1, and SNU-213 human pancreatic cancer cells were incubated with varying doses of kaempferol for 72 h. The viability was measured by WST-1 assay (Data represent the percentage ± SD and are representative of three individual experiments, *<i>p</i> < 0.05, **<i>p</i> < 0.01, ***<i>p</i> < 0.001). (D) Miapaca-2 cells were incubated either in the absence or presence of kaempferol (0, 0.1, and 10 μM) and/or z-VAD (1 μM) for 72 h. Cell lysates were subjected to immunoblot analysis using antibodies against total caspase-3, cleaved-caspase-3, and GAPDH. (E) Panc-1 cells were incubated with different dosages of kaempferol (0, 10, and 100 μM) for 72 h. Cell lysates were subjected to immunoblot analysis using antibodies against PCNA, total caspase-3, cleaved-caspase-3, and GAPDH.</p

The effect of different doses of kaempferol on migration of human pancreatic cancer cells.

<p>(A-D) Miapaca-2, Panc-1, SNU-213 cells, and HUVECs were incubated with varying doses of kaempferol for 6 h. The migration activities were evaluated using the transwell-migration assay (Data represent the percentage ± SD and are representative of three individual experiments, n.s. means non-significant, *<i>p</i> < 0.05, **<i>p</i> < 0.01, ***<i>p</i> < 0.001). (E-G) Miapaca-2, Panc-1, and SNU-213 cells were incubated with varying doses of kaempferol for 20 h. The invasive activities were evaluated using the Transwell-invasion assay assay (data represent the percentage ± SD and are representative of three individual experiments, *<i>p</i> < 0.05, **<i>p</i> < 0.01, ***<i>p</i> < 0.001). (H) Representative image of Trans-well invasion assay (scale bar = 50 μm).</p

Kaempferol mechanism of action to inhibit growth and migration through the blockade of epidermal growth factor receptor-related signaling pathway in human pancreatic cancer cells

<p>Kaempferol mechanism of action to inhibit growth and migration through the blockade of epidermal growth factor receptor-related signaling pathway in human pancreatic cancer cells</p

Structure of kaempferol and its derivatives.

<p>Structure of kaempferol and its derivatives.</p