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Updated: May 10, 2025
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Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
Published on: April 2, 2020
6.3K
Crizotinib Inhibits Viability, Migration, and Invasion by Suppressing the c-Met/PI3K/Akt Pathway in the
Byeongdo Song1, Danhyo Kim2, Jin-Nyoung Ho2
1Department of Urology, Hanyang University Guri Hospital, 153, Gyeongchun-ro, Guri-si 11923, Gyeonggi-do, Republic of Korea.
Current Oncology (Toronto, Ont.)
|April 25, 2025
Summary
Crizotinib effectively suppressed bladder cancer cell growth, migration, and invasion in a 3D model. This tyrosine kinase inhibitor shows promise against both cisplatin-naïve and resistant bladder cancer cells by inhibiting the c-Met/PI3K/Akt pathway.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Bladder cancer (BC) presents challenges, particularly with cisplatin-resistant forms.
- Three-dimensional (3D) cell culture models offer a more realistic platform for evaluating cancer therapies compared to 2D models.
Purpose of the Study:
- To assess the therapeutic potential of crizotinib, a tyrosine kinase inhibitor, against human bladder cancer cells.
- To investigate crizotinib's efficacy using a 3D spheroid cell culture system for both cisplatin-naïve and resistant cell lines.
Main Methods:
- Utilized T24 and T24R2 human BC cell lines to create 3D spheroids.
- Exposed spheroids to varying crizotinib concentrations to determine optimal dosage.
- Analyzed cell proliferation, migration, invasion, gene expression (E-cadherin, vimentin, apoptosis-related genes), and protein levels (p-Met, p-Akt) via qPCR and Western blotting.
Main Results:
- Crizotinib significantly suppressed proliferation, migration, and invasion in both BC cell lines within the 3D model.
- Observed decreased E-cadherin and increased vimentin expression, indicating suppression of epithelial-mesenchymal transition (EMT).
- Noted increased expression of apoptosis-related genes and decreased levels of phosphorylated c-Met and Akt, suggesting c-Met/PI3K/Akt pathway inhibition.
Conclusions:
- Crizotinib demonstrates significant antitumor effects against both cisplatin-naïve and cisplatin-resistant bladder cancer cells.
- The 3D spheroid model provides a more relevant system for evaluating crizotinib's efficacy.
- Crizotinib's therapeutic potential is linked to the inhibition of the c-Met/PI3K/Akt signaling pathway, impacting EMT and promoting apoptosis.
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