論文 - 詳細
| RRC ID | 72482 |
|---|---|
| 著者 | Uwada J, Mukai S, Terada N, Nakazawa H, Islam MS, Nagai T, Fujii M, Yamasaki K, Taniguchi T, Kamoto T, Yazawa T. |
| タイトル | Pleiotropic effects of probenecid on three-dimensional cultures of prostate cancer cells. |
| ジャーナル | Life Sci |
| Abstract |
AIMS:Chemoresistance remains a persistent challenge in advanced prostate cancer therapy. Probenecid reportedly inhibits multiple drug-efflux transporters; hence, it can be employed as a potential sensitizer for chemotherapy. In the present study, we evaluated the effects of probenecid on three-dimensional (3D)-cultures of prostate cancer cells. MAIN METHODS:Prostate cancer cell lines, 22Rv1 and PC-3 were cultured as multicellular tumor spheroids. The effects of probenecid were evaluated using the MTT assay for viability, microscopy for spheroid size, and soft agar colony formation assay for anchorage-independent growth. KEY FINDINGS:The 3D-cultured 22Rv1 cells were less sensitive to cisplatin and doxorubicin than two-dimensional (2D) cell culture. Co-administration of probenecid at a low (100 or 300 μM), but not high (500 μM), concentration increased the sensitivity to cisplatin or doxorubicin in 22Rv1 spheroids. Probenecid increased the expression of ABCG2, a multidrug resistance transporter, in a dose-dependent manner. Furthermore, treatment with probenecid alone reduced the growth of 22Rv1 spheroids. Conversely, probenecid inhibited spheroid compaction rather than growth inhibition in 3D-cultured PC-3 cells. Moreover, probenecid inhibited colony formation of 22Rv1 and PC-3 cells in soft agar, as well as downregulated focal adhesion kinase (FAK), a crucial factor in anchorage-independent growth. SIGNIFICANCE:In 3D-cultured prostate cancer cells, probenecid demonstrated pleiotropic effects such as chemosensitization, growth suppression, inhibition of spheroid compaction, and suppression of anchorage-independent growth. Elucidating the detailed mechanism underlying these probenecid actions could result in the identification of novel therapeutic targets toward the advanced prostate cancer. |
| 巻・号 | 278 |
| ページ | 119554 |
| 公開日 | 2021-8-1 |
| DOI | 10.1016/j.lfs.2021.119554 |
| PII | S0024-3205(21)00540-3 |
| PMID | 33932444 |
| MeSH | Antineoplastic Agents / pharmacology* Cell Proliferation / drug effects Cisplatin / pharmacology* Doxorubicin / pharmacology* Drug Resistance, Neoplasm / drug effects Humans Male PC-3 Cells Probenecid / pharmacology* Prostatic Neoplasms / drug therapy* Prostatic Neoplasms / metabolism Prostatic Neoplasms / pathology Spheroids, Cellular / cytology Spheroids, Cellular / drug effects Spheroids, Cellular / metabolism Spheroids, Cellular / pathology |
| IF | 3.647 |
| リソース情報 | |
| ヒト・動物細胞 | PC-3(RCB2145) |