High Throughput Confined Migration Microfluidic Device for Drug Screening.

Area of Science:

• Oncology
• Biotechnology
• Pharmacology

Background:

• Cancer metastasis, driven by confined tumor cell migration in stiff extracellular matrices, is a leading cause of cancer mortality.
• Existing drugs primarily target unconfined migration, leaving a critical need for inhibitors of confined migration.
• Challenges in studying confined migration include difficult modeling and low-throughput screening methods.

Purpose of the Study:

• To design and validate a multi-functional microfluidic chip for high-throughput drug screening against collective cancer cell migration in confined environments.
• To identify novel compounds that inhibit confined migration across multiple cancer types.

Main Methods:

• Development of a novel microfluidic platform enabling multi-functional drug screening under confined conditions.
• Screening of a 166-compound mechanoreceptor library against hepatocellular carcinoma, non-small lung cancer, breast cancer, and pancreatic ductal adenocarcinoma cells.
• Analysis of drug mechanisms targeting mitochondria, actin polymerization, and cell viability.

Main Results:

• Identification of three compounds—mitochonic acid 5 (MA-5), SB-705498, and diphenyleneiodonium chloride—that significantly inhibit confined migration in pan-cancer cell lines.
• Demonstration of the microfluidic platform's efficacy in high-throughput screening for confined migration inhibitors.
• Elucidation of drug targets including mitochondria, actin polymerization, and cell viability.

Conclusions:

• A high-throughput microfluidic platform for screening drugs targeting confined cancer cell migration has been successfully established.
• Three novel inhibitors of confined migration with potential pan-cancer applications were discovered.
• This platform offers a promising approach for developing new anti-metastasis therapies.