Medeniyet medical journal · 2026
Dual Targeting Strategy: Colchicine and Paclitaxel Combination Against Prostate Cancer Cells Colchicine-Paclitaxel Synergy in Prostate Cancer.
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Sumer Ceren, Sari Ceren, Aras Mertkaya, Usta Duygu Deniz
Аннотация
OBJECTIVE: Prostate cancer is the leading male malignancy. Despite therapeutic advances, drug resistance remains a major obstacle, leading many patients to develop castration-resistant prostate cancer. This study investigates the combined effects of the microtubule-targeting agents colchicine and paclitaxel on DU145 prostate cancer cells.
METHODS: Cell viability was evaluated across a range of doses of colchicine and paclitaxel to determine the IC50, IC30, and IC10 values for each drug. IC10 and IC30 doses of the agents and their combinations were selected for subsequent experiments. The effects of the treatments were then analyzed using the MTT assay, the colony formation assay, the in vitro scratch assay, and acridine orange/ethidium bromide staining.
RESULTS: Monotherapy with colchicine and paclitaxel indicated dose- and time-dependent cytotoxicity in DU145 cells. Notably, IC10 monotherapies had minimal impact on viability, whereas the drug combination produced synergistic inhibition of viability (excess‑over‑Bliss score: 14.8%), along with marked suppression of colony formation and cell motility (p<0.0001). At IC30, the combined treatment nearly abolished colony formation and significantly increased apoptotic and necrotic morphology. These findings reveal that combining sub-therapeutic doses effectively inhibits cell viability, long-term proliferation, and cell motility, where monotherapies are insufficient.
CONCLUSIONS: These preliminary findings demonstrate that the colchicine and paclitaxel combination exhibits potent synergistic effects, particularly at low doses (IC10), and effectively suppresses DU145 prostate cancer cell progression. This dual microtubule-targeting approach may overcome the limitations of monotherapy by significantly inhibiting cell motility and clonogenic survival, while enhancing apoptotic and necrotic cell morphology. Our results suggest that low-dose combination strategies may provide high therapeutic efficacy while minimizing systemic toxicity in the management of advanced prostate cancer.
METHODS: Cell viability was evaluated across a range of doses of colchicine and paclitaxel to determine the IC50, IC30, and IC10 values for each drug. IC10 and IC30 doses of the agents and their combinations were selected for subsequent experiments. The effects of the treatments were then analyzed using the MTT assay, the colony formation assay, the in vitro scratch assay, and acridine orange/ethidium bromide staining.
RESULTS: Monotherapy with colchicine and paclitaxel indicated dose- and time-dependent cytotoxicity in DU145 cells. Notably, IC10 monotherapies had minimal impact on viability, whereas the drug combination produced synergistic inhibition of viability (excess‑over‑Bliss score: 14.8%), along with marked suppression of colony formation and cell motility (p<0.0001). At IC30, the combined treatment nearly abolished colony formation and significantly increased apoptotic and necrotic morphology. These findings reveal that combining sub-therapeutic doses effectively inhibits cell viability, long-term proliferation, and cell motility, where monotherapies are insufficient.
CONCLUSIONS: These preliminary findings demonstrate that the colchicine and paclitaxel combination exhibits potent synergistic effects, particularly at low doses (IC10), and effectively suppresses DU145 prostate cancer cell progression. This dual microtubule-targeting approach may overcome the limitations of monotherapy by significantly inhibiting cell motility and clonogenic survival, while enhancing apoptotic and necrotic cell morphology. Our results suggest that low-dose combination strategies may provide high therapeutic efficacy while minimizing systemic toxicity in the management of advanced prostate cancer.