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Article

Investigating Programmed Cell Death and Tumor Invasion in a Three-Dimensional (3D) Microfluidic Model of Glioblastoma

1
Laboratory for Innovation in Microengineering (LiME), Department of Mechanical Engineering, University of Victoria, 3800 Finnerty Rd., Victoria, BC V8P 2C5, Canada
2
Center for Advanced Materials and Related Technology (CAMTEC), University of Victoria, Victoria, BC V8W 2Y2, Canada
3
Department of Surgery, Queens University, Kingston, ON K7L 2V7, Canada
4
Departments of Human Anatomy and Cell Science, Rady Faculty of Health Science, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
5
The Biology of Breathing Theme, Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(9), 3162; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093162
Received: 31 March 2020 / Revised: 26 April 2020 / Accepted: 28 April 2020 / Published: 30 April 2020
(This article belongs to the Special Issue Recent Advances in Biotechnology)
Glioblastoma multiforme (GBM) is a rapidly progressive and deadly form of brain tumor with a median survival rate of ~15 months. GBMs are hard to treat and significantly affect the patient’s physical and cognitive abilities and quality of life. Temozolomide (TMZ)—an alkylating agent that causes DNA damage—is the only chemotherapy choice for the treatment of GBM. However, TMZ also induces autophagy and causes tumor cell resistance and thus fails to improve the survival rate among patients. Here, we studied the drug-induced programmed cell death and invasion inhibition capacity of TMZ and a mevalonate cascade inhibitor, simvastatin (Simva), in a three-dimensional (3D) microfluidic model of GBM. We elucidate the role of autophagy in apoptotic cell death by comparing apoptosis in autophagy knockdown cells (Atg7 KD) against their scrambled counterparts. Our results show that the cells were significantly less sensitive to drugs in the 3D model as compared to monolayer culture systems. An immunofluorescence analysis confirmed that apoptosis is the mechanism of cell death in TMZ- and Simva-treated glioma cells. However, the induction of apoptosis in the 3D model is significantly lower than in monolayer cultures. We have also shown that autophagy inhibition (Atg7 KD) did not change TMZ and Simva-induced apoptosis in the 3D microfluidic model. Overall, for the first time in this study we have established the simultaneous detection of drug induced apoptosis and autophagy in a 3D microfluidic model of GBM. Our study presents a potential ex vivo platform for developing novel therapeutic strategies tailored toward disrupting key molecular pathways involved in programmed cell death and tumor invasion in glioblastoma. View Full-Text
Keywords: tumor on a chip; glioblastoma; apoptosis; autophagy; cell phenotype; invasion tumor on a chip; glioblastoma; apoptosis; autophagy; cell phenotype; invasion
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MDPI and ACS Style

Samiei, E.; Seyfoori, A.; Toyota, B.; Ghavami, S.; Akbari, M. Investigating Programmed Cell Death and Tumor Invasion in a Three-Dimensional (3D) Microfluidic Model of Glioblastoma. Int. J. Mol. Sci. 2020, 21, 3162. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093162

AMA Style

Samiei E, Seyfoori A, Toyota B, Ghavami S, Akbari M. Investigating Programmed Cell Death and Tumor Invasion in a Three-Dimensional (3D) Microfluidic Model of Glioblastoma. International Journal of Molecular Sciences. 2020; 21(9):3162. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093162

Chicago/Turabian Style

Samiei, Ehsan, Amir Seyfoori, Brian Toyota, Saeid Ghavami, and Mohsen Akbari. 2020. "Investigating Programmed Cell Death and Tumor Invasion in a Three-Dimensional (3D) Microfluidic Model of Glioblastoma" International Journal of Molecular Sciences 21, no. 9: 3162. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093162

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