Key genes and drug delivery systems to improve the efficiency of chemotherapy

Torres‐Martínez, Zally; Delgado, Yamixa; Ferrer-Acosta, Yancy; Suárez-Arroyo, Ivette J.; Joaquin-Ovalle, Freisa; Delinois, Louis J.; Griebenow, Kai

doi:10.20517/cdr.2020.64

Cited by 4 publications

(3 citation statements)

References 225 publications

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“…In the course of evolution, living organisms have developed multiple mechanisms of response to harmful chemicals present in the environment [ 31 ]. Activation of the cell’s defense pathways subsequently leads to an increase in the resistance of cells to various chemicals [ 32 ], often with fundamentally different structures and mechanisms of action, which is called multidrug resistance [ 11 ]. The development of drug resistance, when present in neoplastically transformed human cells, is a real obstacle to anticancer treatment [ 12 ].…”

Section: Cell Resistance To Multiple Drugsmentioning

confidence: 99%

The Roles of microRNAs in Cancer Multidrug Resistance

Pavlíková

Šereš

Breier

et al. 2022

Cancers

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Cancer chemotherapy may induce a multidrug resistance (MDR) phenotype. The development of MDR is based on various molecular causes, of which the following are very common: induction of ABC transporter expression; induction/activation of drug-metabolizing enzymes; alteration of the expression/function of apoptosis-related proteins; changes in cell cycle checkpoints; elevated DNA repair mechanisms. Although these mechanisms of MDR are well described, information on their molecular interaction in overall multidrug resistance is still lacking. MicroRNA (miRNA) expression and subsequent RNA interference are candidates that could be important players in the interplay of MDR mechanisms. The regulation of post-transcriptional processes in the proteosynthetic pathway is considered to be a major function of miRNAs. Due to their complementarity, they are able to bind to target mRNAs, which prevents the mRNAs from interacting effectively with the ribosome, and subsequent degradation of the mRNAs can occur. The aim of this paper is to provide an overview of the possible role of miRNAs in the molecular mechanisms that lead to MDR. The possibility of considering miRNAs as either specific effectors or interesting targets for cancer therapy is also analyzed.

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Section: Cell Resistance To Multiple Drugsmentioning

confidence: 99%

The Roles of microRNAs in Cancer Multidrug Resistance

Pavlíková

Šereš

Breier

et al. 2022

Cancers

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“…There are several types of treatment for GB ( Torres-Martinez et al, 2021 ), of which the standard of care includes surgical resection, followed by RT and concomitant administration of temozolomide (TMZ) ( Fernandes et al, 2017 ). Regardless the addition of secondary treatment using other agents such as receptor tyrosin kinases (RTK) inhibitors and the multidisciplinary treatment, the majority of patients experience a tumor progression with median survival of not more than 15 months ( Stupp et al, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

The effect of Azo-dyes on glioblastoma cells in vitro

Sevastre

Baloi

Alexandru

et al. 2023

Saudi Journal of Biological Sciences

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“…On the other hand, anticancer drugs selectively target fast-replicating cells (13). Another reason for chemotherapy drugs' poor e cacy in hypoxic conditions is the transcription factor HIF 1α, that activates the p53 pathway, which causes apoptosis (14,15).…”

Section: Introductionmentioning

confidence: 99%

Alteration of HIF1a target genes led to 5FU resistance in gastric cancer MKN45 cells under hypoxic condition

Sharifi

Khorashadizadeh

2023

Preprint

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Purpose Gastric cancer (GC) is reported as the fifth most commonly diagnosed cancer and is the fourth most common cause of cancer-associated death in the world. Tumor cell hypoxia is one of the main factors causing 5FU resistance in gastric cancer cells. Herein, we intend to evaluate the efficacy of the 5FU on the MKN45 cell line by establishing an in vitro hypoxic environment and comparing them with results from the normoxic condition. This study aims to evaluate the efficacy of the 5FU on the MKN45 cell line in normoxic and hypoxic conditions. Methods The MKN45 gastric cancer cell line was cultured in normoxic and hypoxic conditions. The cells were treated with various concentrations of 5-FU for 72 h. Then, cell viability was analyzed by the MTT method. Also, the induction of apoptosis was analyzed by flow cytometry. The expression levels of HIF-1 a, P53, BAX, Bcl2, MRP1, and Casp3 genes were quantified by real-time PCR. A statistical analysis of the results was done using SPSS software. Results Our study showed that a hypoxic condition leads to a higher resistance against 5-FU toxicity in MKN45 cells compared to normoxia. As a result of this drug resistance, we also found significantly low apoptotic cells in hypoxic conditions. Data of gene expression in 5-FU treated MKN45 cells, indicated significant up-regulation of HIF1a in hypoxic conditions. We also showed an elevated level of pro-apoptotic genes (Bax and casp3) in the normoxic and hypoxic groups, but this elevation was significantly lower in hypoxia. In contrast, significant down-regulation of the anti-apoptotic gene (Bcl2) was detected just in the normoxic group, while the Bcl2 gene was significantly up-regulated in the hypoxia versus normoxia group. In the case of p53 and MRP1 genes, we found a higher level of gene expression in MKN45 cells treated under normoxic and hypoxic conditions compared to control, while this increase was more significant in hypoxic conditions. There was no significant difference in the level of expression of the MRP1 gene in hypoxic conditions compared to normoxia. Conclusion Altogether, our results demonstrated that the resistance to 5-FU in MKN45 gastric cancer cells might be due to the upregulation of the HIF-1α gene and its regulated downstream target gene under hypoxic conditions.

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Key genes and drug delivery systems to improve the efficiency of chemotherapy

Cited by 4 publications

References 225 publications

The Roles of microRNAs in Cancer Multidrug Resistance

The Roles of microRNAs in Cancer Multidrug Resistance

The effect of Azo-dyes on glioblastoma cells in vitro

Alteration of HIF1a target genes led to 5FU resistance in gastric cancer MKN45 cells under hypoxic condition

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