BSCI-05 REPURPOSING PROPOFOL FOR THE TREATMENT OF BRAIN METASTASES

BACKGROUND: Recent clinical studies suggest beneficial effects of propofol anesthesia on tumor progression and patient survival in solid tumors but reported benefits are modest. One potential reason is the relatively short, single exposure to propofol, limited to the surgical period. Brain metastases (BM) are the most common brain tumors in adults. Metastatic tumors develop following infiltration of the brain from primary tumors such as lung, breast, melanoma, and colorectal cancers. BM are treated with combination therapies, including surgery, radiotherapy, chemotherapy, and immunotherapy, however the prognosis of most patients with BM remains dismal. In this report we investigated the effects of propofol plus radiation on cancer stem cells derived from human lung cancer brain metastases (BM-CSCs) and their cross-talk with microglia. OBJECTIVES: Our hypothesis is that propofol can be repurposed as a treatment of BM in addition to its anesthetic uses. To test this, we first examined the cytotoxic effects of propofol on cancer stem cells established from BM-CSCs alone and with radiation. Also, we studied the effects of propofol on the cross-talk of BM-CSCs and microglia. RESULTS: We found that propofol 1) exerted inhibitory effect on BM-CSCs self-renewal, stemness and cell proliferation; 2) increased cell death of cancer cells but not normal neural elements; 3) sensitized BM-CSCs to radiation; 4) inhibited the pro-tumorigenic BM-CSCs/ microglia cross-talk by promoting M1 phenotypes of co-cultured microglia. CONCLUSIONS: Propofol exerted anti-tumor effects on BM-CSCs including inhibition of cell renewal, proliferation, and mesenchymal transition. Propofol at sensitized BM-GSCs to radiation and at higher concentrations induced cell death. Propofol exerted anti-tumor cytotoxicity also by inhibiting the pro-tumorigenic CSC-microglia cross-talk via secreted extracellular vesicles (EVs). Propofol effects can be exploited as a general anesthetic of choice during tumor resection and should be examined as an anti-tumor agent in sub-anesthetic doses either alone or in combination with radiation.