A microfluidic lung cancer-vascular tumor-on-a-chip model for precise evaluation of anti-invasion therapeutics

Lung cancer remains the single leading cause of cancer-related incidence and mortality worldwide, with approximately 90% of all cancer-related deaths due to tumor invasion and metastasis. However, traditional in vitro and animal models are not able to accurately replicate the biologically complex tumor microenvironment; therefore, they limit the exact evaluation of anti-invasion therapies. In the present study, we designed, fabricated and characterized a lung cancer-vascular tumor-on-a-chip utilizing microfluidic technology following previous studies to replicate tumor growth, invasion and interactions with the extracellular matrix (ECM). We discovered that tumor cell invasion into the ECM is profoundly related to cytoskeletal remodeling. We evaluated the drug-screening potential of this model by evaluating five clinically used anti-invasion agents: paclitaxel; cisplatin; irinotecan; oxaliplatin; and gemcitabine. We discovered that gemcitabine inhibited tumor growth, invasion of tumor cells, cytoskeletal remodeling and the ability to invade the ECM, while oxaliplatin principally inhibited invasion. In addition, we also found the model to be very effective for screening for active compounds derived from traditional Chinese medicine, as demonstrated by the natural compound rocaglamide (ROC-A) which inhibited the invasion of tumor cells in a dose-dependent manner at 50 nM. Taken together, our lung cancer-vascular tumor-on-a-chip provides a sound model for studying tumor invasion and demonstrates potential as a platform for precise evaluation.