Anticancer research · 2025
A Novel Three Small Molecule Inhibitor Combination Therapy For Prostate Cancer.
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Demir Ummuhan, Badoglu Hilal, Cetin Irem Nur, Bener Muhammed Yasar
Аннотация
BACKGROUND/AIM: Prostate cancer is common in elderly men. Single treatment options are inadequate for effective therapy. In this study, three small-molecule inhibitors targeting three different pathways related to stemness were combined to obtain an effective antiproliferative effect on prostate cancer cell lines. These small molecules and their corresponding target were: KJ-Pyr-9 as an inhibitor of MYC proto-oncogene bHLH transcription factor (MYC); pyrvinium pamoate as an inhibitor of WNT; and glasdegib as an inhibitor of Sonic Hedgehog (SHH), which induces stem cell properties of cells.
MATERIALS AND METHODS: Firstly, the half-maximal inhibitory concentration (IC50) and IC25 doses of each drug against the PC-3 cell line and dose optimization for combination of all three drugs were determined. PNT1A cells were used as a healthy control. 3D culture and scratch assays were applied to test efficiency of combined drug treatment.
RESULTS: According to 2D culture results, the combination was synergistic in PC-3 while its effect was minimal in PNT1A. The combined treatment diminished both viability and size of 3D spheroids of PC-3 and LNCaP cells. In addition, the combined treatment reduced the migratory potential of PC-3 and LNCaP cells.
CONCLUSION: The combined treatment proposed in this study is novel and promising in overcoming drug resistance and side-effects of single agents and may herald a new era in the treatment paradigm for prostate cancer.
MATERIALS AND METHODS: Firstly, the half-maximal inhibitory concentration (IC50) and IC25 doses of each drug against the PC-3 cell line and dose optimization for combination of all three drugs were determined. PNT1A cells were used as a healthy control. 3D culture and scratch assays were applied to test efficiency of combined drug treatment.
RESULTS: According to 2D culture results, the combination was synergistic in PC-3 while its effect was minimal in PNT1A. The combined treatment diminished both viability and size of 3D spheroids of PC-3 and LNCaP cells. In addition, the combined treatment reduced the migratory potential of PC-3 and LNCaP cells.
CONCLUSION: The combined treatment proposed in this study is novel and promising in overcoming drug resistance and side-effects of single agents and may herald a new era in the treatment paradigm for prostate cancer.