scholarly journals The Role of Mitochondria in the Chemoresistance of Pancreatic Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 497
Author(s):  
Yibo Fu ◽  
Francesca Ricciardiello ◽  
Gang Yang ◽  
Jiangdong Qiu ◽  
Hua Huang ◽  
...  

The first-line chemotherapies for patients with unresectable pancreatic cancer (PC) are 5-fluorouracil (5-FU) and gemcitabine therapy. However, due to chemoresistance the prognosis of patients with PC has not been significantly improved. Mitochondria are essential organelles in eukaryotes that evolved from aerobic bacteria. In recent years, many studies have shown that mitochondria play important roles in tumorigenesis and may act as chemotherapeutic targets in PC. In addition, according to recent studies, mitochondria may play important roles in the chemoresistance of PC by affecting apoptosis, metabolism, mtDNA metabolism, and mitochondrial dynamics. Interfering with some of these factors in mitochondria may improve the sensitivity of PC cells to chemotherapeutic agents, such as gemcitabine, making mitochondria promising targets for overcoming chemoresistance in PC.

Pancreas ◽  
2002 ◽  
Vol 24 (2) ◽  
pp. 161-168 ◽  
Author(s):  
William J. Thomas ◽  
Deborah L. Thomas ◽  
Joseph A. Knezetic ◽  
Thomas E. Adrian

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 277
Author(s):  
Jungwhoi Lee ◽  
Jungsul Lee ◽  
Woogwang Sim ◽  
Jae-Hoon Kim

Even though the tumour suppressive role of PTEN is well-known, its prognostic implications are ambiguous. The objective of this study was to further explore the function of PTEN expression in human pancreatic cancer. The expression of PTEN has been dominant in various human cancers including pancreatic cancer when compared with their matched normal tissues. The pancreatic cancer cells have been divided into PTEN blockade-susceptible and PTEN blockade-impassible groups dependent on targeting PTEN by altering intracellular signaling. The expression of PTEN has led to varying clinical outcomes of pancreatic cancer based on GEO Series (GSE) data analysis and Liptak’s z analysis. Differential dependency to PTEN blockade has been ascertained based on the expression of polo-like kinase1 PLK1 in pancreatic cancer cells. The prognostic value of PTEN also depends on PLK1 expression in pancreatic cancer. Collectively, the present study provides a rationale for targeting PTEN as a promising therapeutic strategy dependent on PLK1 expressions using a companion biomarker discovery platform.


RNA Biology ◽  
2019 ◽  
Vol 16 (11) ◽  
pp. 1592-1603 ◽  
Author(s):  
Zheng-Lin Ou ◽  
Zhen Luo ◽  
Wei Wei ◽  
Shuai Liang ◽  
Tai-Long Gao ◽  
...  

2017 ◽  
Vol 8 (7) ◽  
pp. e2924-e2924 ◽  
Author(s):  
Yuran Gao ◽  
Zhicheng Zhang ◽  
Kai Li ◽  
Liying Gong ◽  
Qingzhu Yang ◽  
...  

AbstractThe acquisition of epithelial–mesenchymal transition (EMT) and/or existence of a sub-population of cancer stem-like cells (CSC) are associated with malignant behavior and chemoresistance. To identify which factor could promote EMT and CSC formation and uncover the mechanistic role of such factor is important for novel and targeted therapies. In the present study, we found that the long intergenic non-coding RNA linc-DYNC2H1-4 was upregulated in pancreatic cancer cell line BxPC-3-Gem with acquired gemcitabine resistance. Knockdown of linc-DYNC2H1-4 decreased the invasive behavior of BxPC-3-Gem cells while ectopic expression of linc-DYNC2H1-4 promoted the acquisition of EMT and stemness of the parental sensitive cells. Linc-DYNC2H1-4 upregulated ZEB1, the EMT key player, which led to upregulation and downregulation of its targets vimentin and E-cadherin respectively, as well as enhanced the expressions of CSC makers Lin28, Nanog, Sox2 and Oct4. Linc-DYNC2H1-4 is mainly located in the cytosol. Mechanically, it could sponge miR-145 that targetsZEB1,Lin28,Nanog,Sox2,Oct4to restore these EMT and CSC-associated genes expressions. We proved thatMMP3, the nearby gene of linc-DYNC2H1-4 in the sense strand, was also a target of miR-145. Downregulation ofMMP3by miR-145 was reverted by linc-DYNC2H1-4, indicating that competing with miR-145 is one of the mechanisms for linc-DYNC2H1-4 to regulateMMP3. In summary, our results explore the important role of linc-DYNC2H1-4 in the acquisition of EMT and CSC, and the impact it has on gemcitabine resistance in pancreatic cancer cells.


2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Leo L. Chan ◽  
Sherine George ◽  
Irfan Ahmad ◽  
Saujanya L. Gosangari ◽  
Atiya Abbasi ◽  
...  

Chemotherapeutic agents for cancer are highly toxic to healthy tissues and hence alternative medicine avenues are widely researched. Majority of the recent studies on alternative medicine suggested thatAmoora rohitukapossesses considerable antitumor and antibacterial properties. In this work,rohitukaandchittagonga, fractionated with petroleum ether, dichloromethane, and ethanol, were explored for their anticancer potential against two breast cancer (MCF-7 and HTB-126) and three pancreatic cancer (Panc-1, Mia-Paca2, and Capan1). The human foreskin fibroblast, Hs68, was also included. Cytotoxicity of each extract was analyzed using the MTT assay and label-free photonic crystal biosensor assay. A concentration series of each extract was performed on the six cell lines. For MCF-7 cancer cells, thechittagonga(Pet-Ether and CH2Cl2) androhituka(Pet-Ether) extracts induced cytotoxicity; thechittagonga(EtoAC) androhituka(MeOH) extracts did not induce cytotoxicity. For HTB126, Panc-1, Mia-Paca2, and Capan-1 cancer cells, only thechittagongaCH2Cl2extract showed a significant cytotoxic effect. The extracts were not cytotoxic to normal fibroblast Hs68 cells, which may be correlated to the specificity ofAmooraextracts in targeting cancerous cells. Based on these results, further examination of the potential anticancer propertiesAmooraspecies and the identification of the active ingredients of these extracts is warranted.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 224-224 ◽  
Author(s):  
Yoon Ho Ko ◽  
Young-Seok Cho ◽  
Hye Sung Won ◽  
Eun Kyoung Jeon ◽  
Young Seon Hong

224 Background: Autophagy is a catabolic process and provides metabolic support for the cell by degradation of intracellular macromolecules. Various types of stress, including hypoxia, activate autophagy. Recent studies have suggested that hypoxia has been shown to associate with resistance to chemotherapy and radiation therapy and hence poor prognosis in pancreatic cancer. This study investigated the role of autophagy in the treatment of pancreatic cancer with gemcitabine under hypoxic condition. Methods: To evaluate the role of autophagy inhibition in hypoxia-induced chemoresistance, BxPC-3 human pancreatic cancer cell line was used under normoxic and hypoxic conditions.We evaluated the extent of LC3-II, as an autophagosome marker, induced by gemcitabine, by western blotting to measure the hypoxia- or chemotherapy- induced autophagy. We then examined the effects of gemcitabine on induction of apoptosis under normoxic and hypoxic conditions. Next, to determine the effect of 3-MA, a known inhibitor of autophagy, on overcoming hypoxia-induced chemoresistance, the MTS assay and flow cytometry were performed. Results: Compared with normoxia, gemcitabine-induced cell death under hypoxia was significantly decreased, as a result of the reduced apoptosis. Western blotting analysis demonstrated that LC3-II was increased under hypoxia, compared with normoxia.However, we found that 3-MA can enhance the growth inhibition and apoptotic effect of gemcitabine, even under hypoxia. These findings mean that autophagy mediates the chemoresistance under hypoxia. Conclusions: Activated autophagy plays a role in hypoxia-induced chemoresistance of pancreatic cancer cells. These findings may have important implications for future therapeutic strategies using gemcitabine against pancreatic cancer.


Pancreas ◽  
2002 ◽  
Vol 24 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Zan Yao ◽  
Yoshinori Okabayashi ◽  
Yoshihiro Yutsudo ◽  
Tadahiro Kitamura ◽  
Wataru Ogawa ◽  
...  

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