DHFR and MDR1 upregulation is associated with chemoresistance in osteosarcoma stem-like cells

Lee, Yu‐Hsien; Yang, Hui‐Wen; Yang, Li‐Chiu; Lu, Michael S.-C.; Tsai, Lo–Lin; Yang, Shun‐Fa; Huang, Yu‐Feng; Chou, Ming‐Yung; Yu, Cheng–Chia; Hu, Fang‐Wei

doi:10.3892/ol.2017.6132

Cited by 25 publications

(23 citation statements)

References 46 publications

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“…8 70 71 ATP-binding cassette subfamily B member 1 (ABCB1) is a multidrug-resistant (MDR) protein involved in effluxing xenobiotics like drugs, toxins and so on, and its overexpression confers multidrug resistance in malignant tumors including osteosarcoma. 72 In MDR cancer cell, miR-497-mediated attenuation of ABCB1 73 and miR-152 mediated downregulation of c-MET/PI3K/AKT pathway that seemed to upregulate ABCB1 expression 71 74 might serve as a possible molecular link of lncPVT1 with the drug transporter (ABCB1) and associated drug resistance phenomenon. ABCB1 was also considered as downstream oncogenic effector of circPVT1 in OS 53 ; however, the underlying molecular mechanism was not explored.…”

Section: Non-small Cell Lung Carcinomamentioning

confidence: 99%

Circular PVT1: an oncogenic non-coding RNA with emerging clinical importance

et al. 2019

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The importance of circular RNAs (circRNAs) in pathological processes like cancer is evident. Among the circRNAs, recent studies have brought circPVT1 under focus as the most potent oncogenic non-coding RNA. Recent studies on various aspects of circPVT1, including its biogenesis, molecular alteration and its probable role in oncogenesis, have been conducted for research and clinical interest. In this review, a first attempt has been made to summarise the available data on circPVT1 from PubMed and other relevant databases with special emphasis on its role in development, progression and prognosis of various malignant conditions. CircPVT1 is derived from the same genetic locus encoding for long non-coding RNA lncPVT1; however, existing literature suggested circPVT1 and lncPVT1 are transcripted independently by different promoters. The interaction between circRNA and microRNA has been highlighted in majority of the few malignancies in which circPVT1 was studied. Besides its importance in diagnostic and prognostic procedures, circPVT1 seemed to have huge therapeutic potential as evident from differential drug response of cancer cell line as well as primary tumors depending on expression level of the candidate. circPVT1 in cancer therapeutics might be promising as a biomarker to make the existing treatment protocol more effective and also as potential target for designing novel therapeutic intervention.

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Section: Non-small Cell Lung Carcinomamentioning

confidence: 99%

Circular PVT1: an oncogenic non-coding RNA with emerging clinical importance

et al. 2019

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“…TYMS upregulation is associated with an aggressive prostate cancer phenotype and chromosomal deletions 76. DHFR, which catalyses the generation of THF, is overexpressed in osteosarcoma stem-like cells; this overexpression enhances their chemoresistance to methotrexate (MTX) 81. In addition, other THF metabolism enzymes, such as SHMT1, SHMT2, and MTHFD2, are upregulated in cancer to promote DNA synthesis 82-84.…”

Section: Tetrahydrofolate (Thf)mentioning

confidence: 99%

Metabolic Intermediates in Tumorigenesis and Progression

He¹,

Gao²,

Tang³

et al. 2019

Int. J. Biol. Sci.

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Traditional antitumor drugs inhibit the proliferation and metastasis of tumour cells by restraining the replication and expression of DNA. These drugs are usually highly cytotoxic. They kill tumour cells while also cause damage to normal cells at the same time, especially the hematopoietic cells that divide vigorously. Patients are exposed to other serious situations such as a severe infection caused by a decrease in the number of white blood cells. Energy metabolism is an essential process for the survival of all cells, but differs greatly between normal cells and tumour cells in metabolic pathways and metabolic intermediates. Whether this difference could be used as new therapeutic target while reducing damage to normal tissues is the topic of this paper. In this paper, we introduce five major metabolic intermediates in detail, including acetyl-CoA, SAM, FAD, NAD + and THF. Their contents and functions in tumour cells and normal cells are significantly different. And the possible regulatory mechanisms that lead to these differences are proposed carefully. It is hoped that the key enzymes in these regulatory pathways could be used as new targets for tumour therapy.

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“…In several cancer types, increased activity of the drug efflux pumps have been associated with chemoresistance, known as multiple drug resistance [23]. This hinders the efficiency of numerous anticancer drugs which are renowned to specifically target aggressive cancer types.…”

Section: Discussionmentioning

confidence: 99%

Quercetin potentializes the respective cytotoxic activity of gemcitabine or doxorubicin on 3D culture of AsPC-1 or HepG2 cells, through the inhibition of HIF-1α and MDR1

et al. 2020

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The impact of cancer on lifespan is significantly increasing worldwide. Enhanced activity of drug efflux pumps and the incidences of the tumor microenvironment such as the apparition of a hypoxic gradient inside of the bulk tumor, are the major causes of chemotherapy failure. For instance, expression of Hypoxia-inducible factor (HIF-1α) has been associated with metastasis, resistance to chemotherapy and reduced survival rate. One of the current challenges to fight against cancer is therefore to find new molecules with therapeutic potential that could overcome this chemoresistance. In the present study, we focused on the bioactive plant flavonoid quercetin, which has strong antioxidant and anti-proliferative properties. We examined the efficacy of combined treatments of quercetin and the anti-cancer drugs gemcitabine and doxorubicin, known to specifically act on human pancreatic and hepatic cancer cells, respectively. Moreover, our study aimed to investigate more in-depth the implication of the multidrug transporter MDR1 and HIF-1α n chemoresistance and if quercetin could act on the activity of the drug efflux pumps and the hypoxia-associated effects. We observed that the anti-cancer drugs, were more effective when administered in combination with quercetin, as shown by an increased percentage of dead cells up to 60% in both 2D and 3D cultures. In addition, our results indicated that the combination of anti-cancer drugs and quercetin downregulated the expression of HIF-1α and increased the expression levels of the regulator of apoptosis p53. Moreover, we observed that quercetin could inhibit the efflux activity of MDR1. Finally, our in vitro study suggests that the efficiency of the chemotherapeutic activity of known anti-cancer drugs might be significantly increased upon combination with quercetin. This flavonoid may therefore be a promising pharmacological agent for novel combination therapy since it potentializes the cytotoxic activity of gemcitabine and doxorubicin on by targeting the chemoresistance developed by the pancreatic and liver cancer cells respectively.

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DHFR and MDR1 upregulation is associated with chemoresistance in osteosarcoma stem-like cells

Cited by 25 publications

References 46 publications

Circular PVT1: an oncogenic non-coding RNA with emerging clinical importance

Circular PVT1: an oncogenic non-coding RNA with emerging clinical importance

Metabolic Intermediates in Tumorigenesis and Progression

Quercetin potentializes the respective cytotoxic activity of gemcitabine or doxorubicin on 3D culture of AsPC-1 or HepG2 cells, through the inhibition of HIF-1α and MDR1

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