BIOMAT Database Logo BIOMAT Database Logo

The inhibition of heme oxygenase-1 enhances the chemosensitivity and suppresses the proliferation of pancreatic cancer cells through the SHH signaling pathway. 2018

Liang Han, and Jie Jiang, and Qingyong Ma, and Zheng Wu, and Zheng Wang
Department of Hepatobiliary Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Pancreatic cancer (PC) is a type of cancer associated with a high fatality rate due to a poor prognosis and resistance to treatment. Heme oxygenase-1 (HO-1) is significantly overexpressed in a number of types of cancer and seems to play an important role in cancer progression. In this study, we examined the potential effects of HO-1 on PC cell proliferation and sensivity to gemcitabine (Gem). Furthermore, the role of the sonic hedgehog (SHH) signaling pathway in the regulatory effects of HO-1 on PC progression were examined. For this purpose, the expression of HO-1 was examined in cultured PC cells by real-time PCR, western blot analysis and immunofluorescence. Transfection with small interfering RNA against HO-1 or an overexpression plasmid were used to regulate the expression of HO-1 in the MIA PaCa-2 and PANC-1 cell lines. Cell proliferation was examined by MTT assays in response to the different treatments. The results revealed that HO-1 expression differed significantly in the different PC cells. The overexpression of HO-1 induced PC cell proliferation and the inhibition of HO-1 decreased the cell proliferative ability. Furthermore, HO-1 activated the SHH signaling pathway in the PC cells. In addition, the SHH signaling pathway was found to play a role in HO-1-induced PC cell proliferation. The inhibition of HO-1 enhanced the responsiveness of PC cells to Gem and Gem was found to regulate the expression of HO-1 and the activation of the SHH pathway. On the whole, our findings indicate that HO-1 overexpression in PC cells may be responsible for the increased cell proliferation and the resistance to anticancer therapy. Furthermore, the SHH signaling pathway, the activation of which was initiated by HO-1, may be one of the endogenous mechanisms in this process. Our data shed light into the association between HO-1 and SHH in PC cells, and may aid in the development of novel therapeutic targets for the treatment of patients with PC.

UI MeSH Term Description Entries
D010190 Pancreatic Neoplasms Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA). Cancer of Pancreas,Pancreatic Cancer,Cancer of the Pancreas,Neoplasms, Pancreatic,Pancreas Cancer,Pancreas Neoplasms,Pancreatic Acinar Carcinoma,Pancreatic Carcinoma,Acinar Carcinoma, Pancreatic,Acinar Carcinomas, Pancreatic,Cancer, Pancreas,Cancer, Pancreatic,Cancers, Pancreas,Cancers, Pancreatic,Carcinoma, Pancreatic,Carcinoma, Pancreatic Acinar,Carcinomas, Pancreatic,Carcinomas, Pancreatic Acinar,Neoplasm, Pancreas,Neoplasm, Pancreatic,Neoplasms, Pancreas,Pancreas Cancers,Pancreas Neoplasm,Pancreatic Acinar Carcinomas,Pancreatic Cancers,Pancreatic Carcinomas,Pancreatic Neoplasm
D011524 Protoporphyrins Porphyrins with four methyl, two vinyl, and two propionic acid side chains attached to the pyrrole rings. Protoporphyrin IX occurs in hemoglobin, myoglobin, and most of the cytochromes.
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003841 Deoxycytidine A nucleoside component of DNA composed of CYTOSINE and DEOXYRIBOSE. Cytosine Deoxyribonucleoside,Cytosine Deoxyriboside,Deoxyribonucleoside, Cytosine,Deoxyriboside, Cytosine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000093542 Gemcitabine A deoxycytidine antimetabolite used as an antineoplastic agent. 2',2'-Difluoro-2'-Deoxycytidine,2',2'-Difluorodeoxycytidine,2'-Deoxy-2',2''-Difluorocytidine-5'-O-Monophosphate,2'-Deoxy-2'-Difluorocytidine,Gemcitabine Hydrochloride,Gemcitabine, (D-threo-pentafuranosyl)-Isomer,Gemcitabine, (alpha-D-threo-pentofuranosyl)-Isomer,Gemcitabine, (beta-D-threo-pentafuranosyl)-Isomer,Gemicitabine,2',2'-DFDC,Gemzar,LY 188011,LY-188011,dFdCyd,188011, LY,2' Deoxy 2' Difluorocytidine,2' Deoxy 2',2'' Difluorocytidine 5' O Monophosphate,Hydrochloride, Gemcitabine
D014704 Veratrum Alkaloids Alkaloids with powerful hypotensive effects isolated from American or European Hellebore (Veratrum viride Ait. Liliaceae and Veratrum album L. Liliaceae). They increase cholinergic and decrease adrenergic tone with appropriate side effects and at higher doses depress respiration and produce cardiac arrhythmias; only the ester alkaloids have been used as hypotensive agents in specific instances. They have been generally replaced by drugs with fewer adverse effects. Alkaloids, Veratrum
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015854 Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Up-Regulation,Upregulation,Up-Regulation (Physiology),Up Regulation
D015972 Gene Expression Regulation, Neoplastic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue. Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic

Related Publications

Liang Han, and Jie Jiang, and Qingyong Ma, and Zheng Wu, and Zheng Wang
Inhibition of heme oxygenase-1 enhances the chemosensitivity of laryngeal squamous cell cancer Hep-2 cells to cisplatin.
April 2016, Apoptosis : an international journal on programmed cell death,
Liang Han, and Jie Jiang, and Qingyong Ma, and Zheng Wu, and Zheng Wang
Arctigenin enhances chemosensitivity of cancer cells to cisplatin through inhibition of the STAT3 signaling pathway.
October 2011, Journal of cellular biochemistry,
Liang Han, and Jie Jiang, and Qingyong Ma, and Zheng Wu, and Zheng Wang
Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway.
April 2017, Archives of pharmacal research,
Liang Han, and Jie Jiang, and Qingyong Ma, and Zheng Wu, and Zheng Wang
Suppression of Nrf2-driven heme oxygenase-1 enhances the chemosensitivity of lung cancer A549 cells toward cisplatin.
April 2008, Lung cancer (Amsterdam, Netherlands),
Liang Han, and Jie Jiang, and Qingyong Ma, and Zheng Wu, and Zheng Wang
eckol enhances heme oxygenase-1 expression through activation of Nrf2/JNK pathway in HepG2 cells.
September 2014, Molecules (Basel, Switzerland),
Liang Han, and Jie Jiang, and Qingyong Ma, and Zheng Wu, and Zheng Wang
Inhibition of heme oxygenase-1 enhances the cytotoxic effect of gemcitabine in urothelial cancer cells.
June 2010, Anticancer research,
Liang Han, and Jie Jiang, and Qingyong Ma, and Zheng Wu, and Zheng Wang
Heme Oxygenase-1 Suppresses Wnt Signaling Pathway in Nonalcoholic Steatohepatitis-Related Liver Fibrosis.
January 2020, BioMed research international,
Liang Han, and Jie Jiang, and Qingyong Ma, and Zheng Wu, and Zheng Wang
Inhibition of heme oxygenase-1 increases responsiveness of pancreatic cancer cells to anticancer treatment.
May 2005, Clinical cancer research : an official journal of the American Association for Cancer Research,
Liang Han, and Jie Jiang, and Qingyong Ma, and Zheng Wu, and Zheng Wang
Heme oxygenase-1 suppresses the apoptosis of acute myeloid leukemia cells via the JNK/c-JUN signaling pathway.
May 2015, Leukemia research,
Liang Han, and Jie Jiang, and Qingyong Ma, and Zheng Wu, and Zheng Wang
Zinc protoporphyrin suppresses cancer cell viability through a heme oxygenase-1-independent mechanism: the involvement of the Wnt/β-catenin signaling pathway.
June 2013, Biochemical pharmacology,
Copied contents to your clipboard!