プロベネシドが3次元培養された前立腺がん細胞に与える多様な効果

• Published in: 日本薬理学会年会要旨集 p. 1-B-P-078
• Main Authors: 宇和田, 淳介, 中澤, 瞳, 益岡, 尚由
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: cancer; chemotherapy; transporter; uricosuric agent
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.96.0_1-B-P-078

Probenecid, an uricosuric drug, has diverse pharmacological targets, including multidrug resistance-associated protein (MRP). Since inhibition of MRPs contributes to suppression of efflux of anti-cancer drugs, probenecid has been investigated for cancer therapy as a chemosensitizer. In this study, we examined the effects of probenecid on 3D-cultured prostate cancer cells. In the 3D-cultured spheroids of 22Rv1 cells that were less sensitive to cisplatin and doxorubicin than the 2D-cultured monolayer cells, probenecid treatment (100 and 300 μM) increased sensitivity to those anti-cancer drugs. On the other hand, a higher concentration (500 μM) of probenecid showed no chemosensitizing effect, which are consistent with increase in ABCG2, a drug-efflux transporter, at the dose. Furthermore, we found that probenecid has various anti-cancer effects other than alteration of chemosensitivity in 3D culture. Probenecid itself inhibited the viability of 22Rv1 spheroids and suppressed spheroid compaction rather than growth inhibition in the spheroids of another prostate cancer cell line PC-3. In addition, probenecid inhibited colony formation of 22Rv1 and PC-3 cells in soft agar and decreased the protein levels of focal adhesion kinase (FAK), which is important for anchorage-independent growth. In this presentation, we will also discuss about the latest findings including the target of probenecid in these anti-cancer effects.