scholarly journals Expression and Functional Identification of INPP4B in Gallbladder Cancer Patients and Gallbladder Cancer Cells

2020 ◽  
Author(s):  
Youliang Wu ◽  
Delong Meng ◽  
Xin Xu ◽  
Junjun Bao ◽  
Yexiang You ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Cancer Cells ◽  
Clinical Significance ◽  
Negative Regulator ◽  
Inositol Polyphosphate ◽  
Functional Identification ◽  
Human Gallbladder ◽  
Apoptosis Detection ◽  
Normal Gallbladder

Abstract Purpose: Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of PI3K-Akt signaling pathway and plays a contradictory role in different types of cancers. However, its biological role in human gallbladder cancer (GBC) remain unclear. Here we aimed to investigate the expression, clinical significance and biological function of INPP4B in GBC clinical dates and GBC cell lines. Methods: The INPP4B protein expression levels in gallbladder cancer tissues and normal gallbladder tissues were detected by immunohistochemistry, and the clinical significance of INPP4B was analyzed. Knockdown and overexpression of INPP4B on GBC-SD and SGC-996 cells were used to identify INPP4B function in vitro, using cell proliferation assay, clonogenic assay, apoptosis detection, cratch wound-healing assay and transwell assay.Results: INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues, and was related to histopathological differentiation. Here, we observed that INPP4B was highly expressed in high-moderate differentiated compared to low-undifferentiated. Additionally, we found that INPP4B expression was not associated with overall survival in GBC patients and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and prognosis of GBC from histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression at different degrees of differentiation. In addition, INPP4B knockdown inhibited tumorigenicity in vitro, and INPP4B overexpression induced tumorigenicity in vitro, which may play a role as an oncoprotein.Conclusions: These findings implicated that INPP4B may play a dual role in the prognosis of GBC with different degrees of differentiation, and might act as an oncogene in gallbladder cancer cells.

scholarly journals Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Youliang Wu ◽  
Delong Meng ◽  
Xin Xu ◽  
Junjun Bao ◽  
Yexiang You ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Cancer Cells ◽  
Clinical Significance ◽  
Functional Characterization ◽  
Negative Regulator ◽  
Migration And Invasion ◽  
Human Gallbladder ◽  
Normal Gallbladder ◽  
Degree Of Differentiation

Abstract Background Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of the PI3K-Akt signalling pathway and plays a contradictory role in different types of cancers. However, the its biological role played by INPP4B in human gallbladder cancer (GBC) has not been elucidated. In this study, we investigated the expression, clinical significance and biological function of INPP4B in GBC patients and cell lines. Methods The INPP4B protein expression levels in gallbladder cancer tissues and normal gallbladder tissues were detected by immunohistochemistry, and the clinical significance of INPP4B was analysed. Knockdown and overexpression of INPP4B in GBC-SD and SGC-996 cells followed by cell proliferation, clonogenic, apoptosis detection, scratch wound-healing and transwell assays were used to identify INPP4B function in vitro. Results INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues and was related to histopathological differentiation (p = 0.026). Here, we observed that INPP4B was highly expressed in high-moderately differentiated tumours compared with low-undifferentiated tumours (p = 0.022). Additionally, we found that INPP4B expression was not associated with overall survival of GBC patients (p = 0.071) and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and the prognosis of GBC based on histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression depending on the degree of differentiation. In addition, INPP4B knockdown inhibited the proliferation, colony formation, migration and invasion in GBC cells, while INPP4B overexpression had the opposite effects in vitro, which indicates its role as an oncoprotein. Conclusions These findings suggested that INPP4B may play a dual role in the prognosis of GBC depending on the degree of differentiation and that INPP4B might act as an oncogene in gallbladder cancer cells.

scholarly journals Osthole inhibits the progression of human gallbladder cancer cells through JAK/STAT3 signal pathway both in vitro and in vivo

2019 ◽  
Vol 30 (10) ◽  
pp. 1022-1030 ◽  
Author(s):  
Tian Le Zou ◽  
Hong Fei Wang ◽  
Tai Ren ◽  
Zi Yu Shao ◽  
Rui Yan Yuan ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Cancer Cells ◽  
Signal Pathway ◽  
Human Gallbladder

Cytotoxic Effect of the Combination of Gemcitabine and Atorvastatin Loaded in Microemulsion on the HCT116 Colon Cancer Cells

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Therapeutic Potential ◽  
Morphological Changes ◽  
In Vitro Study ◽  
Colon Cancer Cells ◽  
Apoptosis Detection ◽  
Hct116 Cells

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

scholarly journals Growth Inhibition of Refractory Human Gallbladder Cancer Cells by Retinol, and Its Mechanism of Action

2017 ◽  
Vol 40 (4) ◽  
pp. 495-503 ◽  
Author(s):  
Chuan Li ◽  
Masahiko Imai ◽  
Shinya Hasegawa ◽  
Masahiro Yamasaki ◽  
Noriko Takahashi
Keyword(s):  
Growth Inhibition ◽  
Gallbladder Cancer ◽  
Cancer Cells ◽  
Mechanism Of Action ◽  
Human Gallbladder

scholarly journals MBD1 promotes the malignant behavior of gallbladder cancer cells and induces chemotherapeutic resistance to gemcitabine

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Liu Wensheng ◽  
Zhang Bo ◽  
Hu Qiangsheng ◽  
Xu Wenyan ◽  
Ji Shunrong ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Viability ◽  
Gallbladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Human Gallbladder ◽  
Mesenchymal Transition ◽  
Cancer Tissues

Abstract Background Methyl-CpG binding domain protein 1 (MBD1), which couples DNA methylation to transcriptional repression, has been implicated in transcriptional regulation, heterochromatin formation, genomic stability, cell cycle progression and development. It has also been proven that MBD1 is involved in tumor development and progression. However, whether MBD1 is involved in tumorigenesis, especially in gallbladder cancer, is totally unknown. Methods Human GBC-SD and SGC996 cells were used to perform experiments. Invasion, wound healing and colony formation assays were performed to evaluate cell viability. A CCK-8 assay was performed to assess gallbladder cancer cell viability after gemcitabine treatment. Western blot analysis was used to evaluate changes in protein expression. Human gallbladder cancer tissues and adjacent nontumor tissues were subjected to immunohistochemical staining to detect protein expression. Results We found that MBD1 expression was significantly upregulated in gallbladder cancer tissues compared with that in surrounding normal tissues according to immunohistochemical analysis of 84 surgically resected gallbladder cancer specimens. These data also indicated that higher MBD1 expression was correlated with lymph node metastasis and poor survival in gallbladder cancer patients. Overexpression and deletion in vitro validated MBD1 as a potent oncogene promoting malignant behaviors in gallbladder cancer cells, including invasion, proliferation and migration, as well as epithelial–mesenchymal transition. Studies have demonstrated that epithelial–mesenchymal transition is common in gallbladder cancer, and it is well known that drug resistance and epithelial–mesenchymal transition are very closely correlated. Herein, our data show that targeting MBD1 restored gallbladder cancer cell sensitivity to gemcitabine chemotherapy. Conclusions Taken together, the results of our study revealed a novel function of MBD1 in gallbladder cancer tumor development and progression through participation in the gallbladder cancer epithelial–mesenchymal transition program, which is involved in resistance to gemcitabine chemotherapy. Thus, MBD1 may be a potential therapeutic target for gallbladder cancer.

scholarly journals Pretreatment with Gemcitabine/5-Fluorouracil Enhances the Cytotoxicity of Trastuzumab to HER2-Negative Human Gallbladder Cancer Cells In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Wei Wang ◽  
Zhenhua Hu ◽  
Yu Huang ◽  
Huilin Zheng ◽  
Qiang Sun ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
In Vitro Study ◽  
Sequential Therapy ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Human Gallbladder ◽  
Phosphorylated Akt

The effects of standard clinical therapies including surgery and chemotherapy are poor in advanced gallbladder cancer (GBC). There are a few reported cases of human epidermal growth factor receptor 2 (HER2)-positive GBC that responded well to trastuzumab. But trastuzumab has not yet been used to treat HER2-negative GBC. In this study, we investigated the cytotoxic effects of different combined therapies with trastuzumab and gemcitabine and/or 5-fluorouracil on HER2-negative GBC cell lines in vitro and in vivo. Trastuzumab alone showed almost no cytotoxicity to GBC cells with originally low HER2 gene amplification. Sequential therapy with chemotherapy followed by trastuzumab showed superiority over reverse sequential chemotherapy (P<0.05), concurrent combined chemotherapy (P<0.05), chemotherapy alone (P<0.05), and trastuzumab alone (P<0.05) in terms of cytotoxicity. Sequential therapy with chemotherapy followed by trastuzumab nearly completely inhibited cell viability in HER2-negative GBC cells. Similar results were observed with regard to apoptosis. Western blot analysis showed that gemcitabine/5-fluorouracil increased the expressions of total and phosphorylated forms of HER2, thus enhancing the cytotoxicity of trastuzumab. In vivo study verified the results of in vitro study by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay and immunohistochemical analysis. Moreover, not only the lightest tumor bearing but also the best survival state was detected in sequential therapy with chemotherapy followed by trastuzumab group compared with other groups. Our in vivo and in vitro data suggest that sequential therapy with gemcitabine/5-fluorouracil followed by trastuzumab represents a novel and promising therapeutic strategy against HER2-negative GBC. The upregulation of phosphorylated HER2 and phosphorylated-AKT induced by gemcitabine/5-fluorouracil treatment shows that HER2/AKT pathway is triggered.

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