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Mechanical effects modulate drug resistance in MCF-7-derived organoids: Insights into the wnt/β-catenin pathway
Seyed Ali Karimifard1, Ali Salehzadeh-Yazdi2, Reza Taghizadeh-Tabarsi1
1Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, 45137-66731, Iran.
Abstract:
Addressing drug resistance poses a significant challenge in cancer treatment, as cancer cells develop diverse mechanisms to evade chemotherapy drugs, leading to treatment failure and disease relapse. Three-dimensional (3D) cell culture has emerged as a valuable model for studying drug resistance, although the underlying mechanisms remain elusive. By obtaining a better understanding of drug resistance within the 3D culture environment, we can develop more effective strategies to overcome it and improve the success of cancer treatments. Notably, the physical structure undergoes notable changes in 3D culture, with mechanical effects believed to play a pivotal role in drug resistance. Hence, our study aimed to explore the influence of mechanical effects on drug resistance by analyzing data related to "drug resistance" and "mechanobiology". Through this analysis, we identified β-catenin and JNK1 as potential factors, which were further examined in MCF-7 cells cultivated under both 2D and 3D culture conditions. Our findings demonstrate that β-catenin is activated through canonical and non-canonical pathways and associated with the drug resistance, particularly in organoids obtained under 3D culture.
Insights
Three-dimensional (3D) cell cultures reveal that mechanical forces influence cancer drug resistance. The study identifies beta-catenin (β-catenin) as a key factor activated in 3D cultures, impacting treatment efficacy.
Area of Science:
- Oncology
- Cell Biology
- Biophysics
Background:
- Cancer drug resistance is a major obstacle in treatment, leading to relapse.
- Three-dimensional (3D) cell culture models offer insights into drug resistance mechanisms.
- Mechanical forces in 3D cultures are hypothesized to influence drug resistance.
Purpose of the Study:
- To investigate the role of mechanical effects in cancer drug resistance.
- To identify molecular factors involved in drug resistance within 3D culture environments.
- To explore the activation pathways of identified factors in different culture conditions.
Main Methods:
- Analysis of data related to drug resistance and mechanobiology.
- Examination of beta-catenin (β-catenin) and JNK1 in MCF-7 cells.
- Comparison of 2D and 3D cell culture models, including organoids.
Main Results:
- Beta-catenin (β-catenin) was identified as a potential factor in drug resistance.
- Beta-catenin (β-catenin) activation was observed through both canonical and non-canonical pathways.
- Enhanced drug resistance was associated with beta-catenin (β-catenin) in 3D-cultured organoids.
Conclusions:
- Mechanical effects in 3D cell culture significantly influence cancer drug resistance.
- Beta-catenin (β-catenin) plays a crucial role in mediating drug resistance in 3D environments.
- Targeting beta-catenin (β-catenin) pathways may offer novel strategies to overcome drug resistance in cancer therapy.
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