Microengineered 3D Tumor Models for Anti-Cancer Drug Discovery in Female-Related Cancers

Amirghasemi, Farbod; Adjei-Sowah, Emmanuela; Pockaj, Barbara A.; Nikkhah, Mehdi

doi:10.1007/s10439-020-02704-9

Cited by 15 publications

(10 citation statements)

References 179 publications

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“…Accumulating evidence has shown that the 3D model is a promising in vitro model for disease modeling and drug discovery ( 26 - 29 ). New cancer drug approval rates are ≤5%, which is significantly lower than that of other therapeutic areas due to lack of effective in vitro screening models ( 30 ). In the present study, two kinds of spheroids were constructed using the U266 and KMS27 MM cell lines.…”

Section: Discussionmentioning

confidence: 99%

Palbociclib regulates the expression of dihydrofolate reductase and the cell cycle to inhibit t (11;14) multiple myeloma

Wang¹,

Wang²,

Wang³

2022

Ann Transl Med

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Background Multiple myeloma (MM) with t (11;14) has a unique biology. New combinations of novel agents are needed to improve the prognosis of patients with t (11;14) MM. As a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), palbociclib (PAL) has been used to treat various malignancies, including breast cancer, ovarian cancer, and so on. However, the effects of PAL on MM remain unclear, and thus, further investigations are warranted. Methods Two t (11;14) MM cell lines, U266 and KMS27, were used in this study. The cell viability and cell cycle were detected to evaluate the anti-myeloma effect of the combination of pralatrexate (PTX) and methotrexate (MTX) with PAL. Three-dimensional (3D) spheroid and mouse models were built to verify the effect of the combination treatment. Western blot was used to detect the expressions of Minichromosome Maintenance Complex Component 2 (MCM2), Minichromosome Maintenance Complex Component 3 (MCM3), and dihydrofolate reductase (DHFR). Results It was observed that PAL had obvious anticancer effects on U266 and KMS27 cells, which had synergistic effects together with PTX and MTX. Importantly, it was found that PAL could promote cell cycle genes including MCM2 and MCM3, and increase the number of MM cells in the G1 phase. Moreover, PAL reduced the expression level of DHFR and exerted its anticancer effects on MM cells by targeting DHFR. It was also determined that PAL exerted anticancer effects on MM in the spheroid and mouse models. Conclusions PAL exerted obvious anticancer effects on t (11;14) MM cells, which had synergistic effects together with PTX and MTX. PAL could promote cell cycle genes and the G1 phase of MM cells. Moreover, PAL reduced the expression level of DHFR and exerted its anticancer effects on t (11;14) MM cells by targeting DHFR.

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Section: Discussionmentioning

confidence: 99%

Palbociclib regulates the expression of dihydrofolate reductase and the cell cycle to inhibit t (11;14) multiple myeloma

Wang¹,

Wang²,

Wang³

2022

Ann Transl Med

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“…Gene expressions in the cells are susceptible to respond to even slight alterations in their microenvironment. Because of the physiological interactions with neighboring cells in 3D models, gene expression of cells is highly reproducible with minor modifications in 3D cultures ( 89 ). Spheroids of glioblastoma grown in 3D conditions are used in examining the different expressions of various genes, which play a vital role in tumor biosynthesis, metabolism, cell architecture, cellular transport, and signal transduction.…”

Section: D Cell Culture-based Gene Expression Studies Of Cancermentioning

confidence: 99%

Implications of Three-Dimensional Cell Culture in Cancer Therapeutic Research

et al. 2022

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Replicating the naturalistic biomechanical milieu of cells is a primary requisite to uncover the fundamental life processes. The native milieu is significantly not replicated in the two-dimensional (2D) cell cultures. Alternatively, the current three-dimensional (3D) culture techniques can replicate the properties of extracellular matrix (ECM), though the recreation of the original microenvironment is challenging. The organization of cells in a 3D manner contributes to better insight about the tumorigenesis mechanism of the in vitro cancer models. Gene expression studies are susceptible to alterations in their microenvironment. Physiological interactions among neighboring cells also contribute to gene expression, which is highly replicable with minor modifications in 3D cultures. 3D cell culture provides a useful platform for identifying the biological characteristics of tumor cells, particularly in the drug sensitivity area of translational medicine. It promises to be a bridge between traditional 2D culture and animal experiments and is of great importance for further research in tumor biology. The new imaging technology and the implementation of standard protocols can address the barriers interfering with the live cell observation in a natural 3D physiological environment.

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“…It is essential to guarantee that the key features of the native tumor are retained to establish accurate and effective methods for the delivery, discovery, and development of anti-cancer drugs. 222 Offering fast and affordable on-chip biomedical research, especially disease detection and monitoring, is a key move in the battle against outbreaks, such as the COVID-19 pandemic that we have been facing. 223 OoC devices can ultimately be generated worldwide without significant cost and can be used as a personalized methods to deliver a range of drugs and vaccines.…”

Section: Future Trends and Limitationsmentioning

confidence: 99%