SLC39A1 Contributes to Gemcitabine Resistance of Pancreatic Ductal Adenocarcinoma by Activating AMPK Signaling

2021 ◽  
Author(s):  
Hao Yu ◽  
Xiaoping Mei ◽  
Xueming Zhang ◽  
Neng Qian ◽  
Qingjiang Yu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Expression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Western Blotting ◽  
Poor Prognosis ◽  
Ductal Adenocarcinoma ◽  
Tumor Type ◽  
Ampk Signaling ◽  
Gemcitabine Resistance ◽  
Mrna And Protein Expression

Abstract Objective: Pancreatic ductal adenocarcinoma (PDAC) serves as a prevailing tumor type with high mortality and poor prognosis. The study aims to explore the mechanism of gemcitabine resistance in PDAC patients. Methods: Immunohistochemistry(IHC)was used to analyze the expression of SLC39A1 in PDAC samples. PDAC cells were culture and transfected with siSLC39A1 and siNC, respectively. Cell proliferation analysis was performed using CCK-8 assay. And qPCR and Western blotting was used to analysis the expression level of SLC39A1 and related signal molecular in cells. Results: IHC results demonstrated that the SLC39A1 expression was significantly up-regulated in the gemcitabine-resistant PDAC samples compared with gemcitabine-sensitive PDAC samples. The treatment of gemcitabine dose-dependently inhibited the viability of the PDAC cells. Meanwhile, the mRNA and protein expression of SLC39A1 were elevated in the gemcitabine-resistant PDAC. The treatment of gemcitabine remarkably decreased viability of PDACs, in which SLC39A1 depletion could reverse this effect. SLC39A1 knockdown could reverse the gemcitabine-induced phosphorylation of AMPK enhanced and gemcitabine-inhibited S6K expression. Conclusion: SLC39A1 contributed to gemcitabine resistance of PDAC by activating AMPK signaling.

scholarly journals High JAK2 Protein Expression Predicts a Poor Prognosis in Patients with Resectable Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yang Song ◽  
Mei-Yue Tang ◽  
Wei Chen ◽  
Zhe Wang ◽  
Si-Liang Wang
Keyword(s):  
Protein Expression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Survival Curve ◽  
Clinicopathological Features ◽  
Ductal Adenocarcinoma ◽  
Clinicopathological Analysis ◽  
Primary Focus ◽  
The Relationship

Background. Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. The JAK/STAT signaling pathway is involved in pancreatic cancer tumorigenesis. However, the prognostic value of JAK2 expression in resectable PDAC is unclear. Method. In this study, we performed a clinicopathological analysis of 62 resectable PDAC cases with a primary focus on survival. JAK2 expression was examined by immunohistochemistry. The relationship between JAK2 expression and clinicopathological features and prognosis was analyzed. Results. Survival curve analyses revealed that high levels of JAK2 expression predict a poor prognosis in resectable PDAC patients. Multivariate analysis confirmed that JAK2 expression can predict the prognosis of PDAC. Conclusions. Assessment of JAK2 protein expression may be a promising method to predict prognosis in patients with resectable PDAC.

scholarly journals High Expression of FAM83B Predicts Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma and Correlates with Cell Cycle and Cell Proliferation

2017 ◽  
Vol 8 (16) ◽  
pp. 3154-3165 ◽  
Author(s):  
Chao-qin Shen ◽  
Ting-Ting Yan ◽  
Wei Liu ◽  
Xiao-qiang Zhu ◽  
Xiang-long Tian ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
High Expression ◽  
Ductal Adenocarcinoma

scholarly journals The clinicopathological significance of forkhead box P1 and forkhead box O3a in pancreatic ductal adenocarcinomas

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769912 ◽  
Author(s):  
Xin Luo ◽  
Zhulin Yang ◽  
Xiao Liu ◽  
Ziru Liu ◽  
Xiongying Miao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Ductal Adenocarcinoma ◽  
Tumor Node Metastasis ◽  
Tumor Mass ◽  
Node Metastasis ◽  
Forkhead Box ◽  
Stage Disease ◽  
Forkhead Box O3a

Pancreatic ductal adenocarcinoma is a highly malignant tumor with poor prognosis, and the biomarkers for the early diagnosis, targeting therapy, and prognosis are still not clinically available. This study investigated the expression of forkhead box P1 and forkhead box O3a proteins in human pancreatic ductal adenocarcinoma tumor tissues and pancreatic tissues with and without benign lesions using immunohistochemical staining. Results showed that the positive rates of forkhead box P1 and forkhead box O3a protein expression were significantly lower in pancreatic ductal adenocarcinoma tumors compared to peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (p < 0.01). Pancreatic tissues with negative forkhead box P1 and forkhead box O3a protein expression exhibited dysplasia or intraepithelial neoplasia. The positive rates of forkhead box P1 and forkhead box O3a expression were significantly lower in cases with tumor mass >5 cm, lymph node metastasis, invasion to surrounding tissues and organs, and tumor–node–metastasis III + IV stage disease compared to cases with tumor mass ⩽5 cm (p < 0.05), no lymph node metastasis (p < 0.001 and p = 0.001, respectively), no invasion (p = 0.003 and p = 0.004, respectively), and tumor–node–metastasis I or II stage disease (p < 0.05). Kaplan–Meier survival analysis showed that pancreatic ductal adenocarcinoma patients with negative forkhead box P1 and forkhead box O3a expression survived significantly shorter than patients with positive forkhead box P1 and forkhead box O3a expression (p = 0.000). Cox multivariate analysis revealed that negative forkhead box P1 and forkhead box O3a expression was an independent poor prognosis factor in pancreatic ductal adenocarcinoma patients. The area under the curve of a receiver operating characteristic curve was 0.642 for forkhead box P1 (95% confidence interval: 0.553–0.730) and 0.655 for forkhead box O3a (95% confidence interval: 0.6568–0.742). Loss of forkhead box P1 and forkhead box O3a protein expression is associated with carcinogenesis, progression, and poor prognosis in patients with pancreatic ductal adenocarcinomas.

scholarly journals BRD4 promotes pancreatic ductal adenocarcinoma cell proliferation and enhances gemcitabine resistance

2015 ◽  
Vol 33 (4) ◽  
pp. 1699-1706 ◽  
Author(s):  
YONG-HUI WANG ◽  
YA-NA SUI ◽  
KAI YAN ◽  
LI-SHAN WANG ◽  
FEI WANG ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Adenocarcinoma Cell ◽  
Gemcitabine Resistance

scholarly journals MicroRNA-183 is involved in cell proliferation, survival and poor prognosis in pancreatic ductal adenocarcinoma by regulating Bmi-1

2014 ◽  
Vol 32 (4) ◽  
pp. 1734-1740 ◽  
Author(s):  
LIANG ZHOU ◽  
WEI-GUO ZHANG ◽  
DE-SHENG WANG ◽  
KAI-SHAN TAO ◽  
WEN-JIE SONG ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Ductal Adenocarcinoma

Icariin Stimulates hFOB 1.19 Osteoblast Proliferation and Differentiation via OPG/RANKL Mediated by the Estrogen Receptor

2020 ◽  
Vol 22 (1) ◽  
pp. 168-175 ◽  
Author(s):  
Lin-Jun Sun ◽  
Chong Li ◽  
Xiang-hao Wen ◽  
Lu Guo ◽  
Zi-Fen Guo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Protein Expression ◽  
Chinese Herb ◽  
Human Osteoblast ◽  
Osteoblast Cells ◽  
Expression Ratio ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mrna And Protein Expression

Background:: Icariin (ICA), one of the main effective components isolated from the traditional Chinese herb Epimedium brevicornu Maxim., has been reported to possess extensive pharmacological actions, including enhanced sexual function, immune regulation, anti-inflammation, and antiosteoporosis. Methods:: Our study was designed to investigate the effect of ICA on cell proliferation and differentiation and the molecular mechanism of OPG/RANKL mediated by the Estrogen Receptor (ER) in hFOB1.19 human osteoblast cells. Results:: The experimental results show that ICA can stimulate cell proliferation and increase the activity of Alkaline Phosphatase (ALP), Osteocalcin (BGP) and I Collagen (Col I) and a number of calcified nodules. Furthermore, the mRNA and protein expression of OPG and RANKL and the OPG/ RANKL mRNA and protein expression ratios were upregulated by ICA. The above-mentioned results indicated that the optimal concentration of ICA for stimulating osteogenesis was 50ng/mL. Subsequent mechanistic studies comparing 50ng/mL ICA with an estrogen receptor antagonist demonstrated that the effect of the upregulated expression is connected with the estrogen receptor. In conclusion, ICA can regulate bone formation by promoting cell proliferation and differentiation and upregulating the OPG/RANKL expression ratio by the ER in hFOB1.19 human osteoblast cells.

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