Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers

Zhang, Lei; Ye, Biwei; Chen, Zhuo; Chen, Zhe‐Sheng

doi:10.1016/j.apsb.2022.10.002

Cited by 37 publications

(18 citation statements)

References 196 publications

(275 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the relationship between methylation and gene expression varies from gene to gene. We found that DNA methylation of the ATP2A2 gene, which is associated with tumor multi‐drug resistance, [ 19 ] negatively regulated gene expression (Figure 3E), whereas gene expression of the SLK gene, which is the target of the leukemia therapeutic drug dasatinib, [ 20 ] was positively correlated with DNA methylation levels (Figure 3F). These findings collectively indicate significant involvement of DNA methylation in gene expression regulation, although it is not the sole determinant.…”

Section: Resultsmentioning

confidence: 99%

DIRECT: Digital Microfluidics for Isolation‐Free Shared Library Construction of Single‐Cell DNA Methylome and Transcriptome

Zeng,

Jiang,

Zhong

et al. 2023

Small Methods

View full text Add to dashboard Cite

Simultaneous profiling of DNA methylation and gene expression within single cells is a powerful technology to dissect complex gene regulatory network of cells. However, existing methods are based on picking a single‐cell in a tube and split single‐cell lysate into two parts for transcriptome and methylome library construction, respectively, which is costly and cumbersome. Here, DIRECT is proposed, a digital microfluidics‐based method for high‐efficiency single‐cell isolation and simultaneous analysis of the methylome and transcriptome in a single library construction. The accuracy of DIRECT is demonstrated in comparison with bulk and single‐omics data, and the high CpG site coverage of DIRECT allows for precise analysis of copy number variation information, enabling expansion of single cell analysis from two‐ to three‐omics. By applying DIRECT to monitor the dynamics of mouse embryonic stem cell differentiation, the relationship between DNA methylation and changes in gene expression during differentiation is revealed. DIRECT enables accurate, robust, and reproducible single‐cell DNA methylation and gene expression co‐analysis in a more cost‐effective, simpler library preparation and automated manner, broadening the application scenarios of single‐cell multi‐omics analysis and revealing a more comprehensive and fine‐grained map of cellular regulatory landscapes.

show abstract

Section: Resultsmentioning

confidence: 99%

DIRECT: Digital Microfluidics for Isolation‐Free Shared Library Construction of Single‐Cell DNA Methylome and Transcriptome

Zeng,

Jiang,

Zhong

et al. 2023

Small Methods

View full text Add to dashboard Cite

show abstract

“…At the transporter level, the levels of BCRP and ABCC10 (i.e., multidrug resistance-associated protein 7, MRP7) in target cells were directly associated with FTO levels in EVs. Changes in m 6 A levels in the ABCC10 gene were also demonstrated experimentally; m 6 A levels in the ABCG2 gene (codifying BCRP) were not investigated [168]. Altogether, FTO-carrying EVs released from drug-resistant cells appear to result in FTO upregulation in drug-sensitive cells.…”

Section: Regulatory Proteinsmentioning

confidence: 92%

“…In line with this, FTO was overexpressed in serum EVs from gefitinib-resistant lung cancer patients compared to serum EVs from gefitinib-sensitive patients. Also, treatment of PC9 gefitinib-sensitive cells with PC9/GR and H1975 EVs increased resistance to the drug, concomitant with a decrease in m 6 A content in target cells. Since the effect was prevented by FTO knockdown in donor cells, a major role of FTO carried by EVs can be proposed.…”

Section: Regulatory Proteinsmentioning

confidence: 98%

Extracellular Vesicles and Cancer Multidrug Resistance: Undesirable Intercellular Messengers?

Bucci-Muñoz

Gola

Rigalli

et al. 2023

Life

View full text Add to dashboard Cite

Cancer multidrug resistance (MDR) is one of the main mechanisms contributing to therapy failure and mortality. Overexpression of drug transporters of the ABC family (ATP-binding cassette) is a major cause of MDR. Extracellular vesicles (EVs) are nanoparticles released by most cells of the organism involved in cell–cell communication. Their cargo mainly comprises, proteins, nucleic acids, and lipids, which are transferred from a donor cell to a target cell and lead to phenotypical changes. In this article, we review the scientific evidence addressing the regulation of ABC transporters by EV-mediated cell–cell communication. MDR transfer from drug-resistant to drug-sensitive cells has been identified in several tumor entities. This was attributed, in some cases, to the direct shuttle of transporter molecules or its coding mRNA between cells. Also, EV-mediated transport of regulatory proteins (e.g., transcription factors) and noncoding RNAs have been indicated to induce MDR. Conversely, the transfer of a drug-sensitive phenotype via EVs has also been reported. Additionally, interactions between non-tumor cells and the tumor cells with an impact on MDR are presented. Finally, we highlight uninvestigated aspects and possible approaches to exploiting this knowledge toward the identification of druggable processes and molecules and, ultimately, the development of novel therapeutic strategies.

show abstract

“…Chemotherapy is the main means of cancer clinical treatment, and the emergence of multidrug resistance (MDR) is the bottleneck problem that may lead to chemotherapy failure and tumor recurrence [1,2]. The aberrant redox homeostasis with both reactive oxide species (ROS) production and antioxidant modulators (e.g.…”

Section: Introductionmentioning

confidence: 99%

Progressive enhanced photodynamic therapy and enhanced chemotherapy fighting against malignant tumors with sequential drug release

Yang,

Zhang,

Bai

et al. 2024

Biomed. Mater.

View full text Add to dashboard Cite

During the process of malignant tumor treatment, photodynamic therapy (PDT) exerts poor efficacy due to the hypoxic environment of the tumor cells, and long-time chemotherapy reduces the sensitivity of tumor cells to chemotherapy drugs due to the presence of drug-resistant proteins on the cell membranes for drug outward transportation. Therefore, we reported a nano platform based on mesoporous silica coated with polydopamine (MSN@PDA) loading PDT enhancer MnO2, photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) (designated as DMPIM) to achieve a sequential release of different drugs for synergistic treatment of malignant tumors. MSN was first synthesized by a template method, then DOX was loaded into the mesoporous channels of MSN, and locked by the PDA coating. Next, ICG was modified by π - π stacking on PDA, and finally, MnO2 layer was accumulated on the surface of DOX@MSN@PDA-ICG@MnO2, achieving orthogonal loading and sequential release of different drugs. DMPIM first generated oxygen (O2) through the reaction between MnO2 and H2O2 after entering tumor cells, alleviating the hypoxic environment of tumors and enhancing the PDT effect of sequentially released ICG. Afterwards, ICG reacted with O2 in tumor tissue to produce reactive oxygen species (ROS), promoting lysosomal escape of drugs and inactivation of p-glycoprotein (p-gp) on tumor cell membranes. DOX loaded in the MSN channels exhibited a delay of approximately 8 hours after ICG release to exert the enhanced chemotherapy effect. The drug delivery system achieved effective sequential release and multimodal combination therapy, which achieved ideal therapeutic effects on malignant tumors. This work offers a route to a sequential drug release for advancing the treatment of malignant tumors.

show abstract

Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers

Cited by 37 publications

References 196 publications

DIRECT: Digital Microfluidics for Isolation‐Free Shared Library Construction of Single‐Cell DNA Methylome and Transcriptome

DIRECT: Digital Microfluidics for Isolation‐Free Shared Library Construction of Single‐Cell DNA Methylome and Transcriptome

Extracellular Vesicles and Cancer Multidrug Resistance: Undesirable Intercellular Messengers?

Progressive enhanced photodynamic therapy and enhanced chemotherapy fighting against malignant tumors with sequential drug release

Contact Info

Product

Resources

About