Emetine reduces the effective dose of cisplatin or carboplatin required to inhibit bladder cancer cell proliferation

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Abstract

OBJECTIVE: We analyzed a novel therapeutic combination of emetine dihydrochloride added to standard of care chemotherapeutic agents (cisplatin, carboplatin, gemcitabine) in human muscle-invasive bladder cancer cell lines to determine if emetine enhanced their anti-tumor activity.

METHODS: Cells were treated with emetine, cisplatin (or carboplatin), and gemcitabine for 24–96 h in vitro. Cell proliferation, apoptosis, autophagy, cell cycle distribution and colony formation were analyzed.

RESULTS: Addition of low dose emetine enhanced the anti-proliferative activity of cisplatin-gemcitabine and carboplatin-gemcitabine against muscle-invasive bladder cancer, but not normal urothelial cells. Importantly, lower doses of cisplatin and carboplatin were required to achieve significant growth inhibition when emetine was included in the therapy. Treatment resulted in a combination of growth arrest, apoptosis and autophagy.

CONCLUSIONS: The inclusion of low dose emetine as part of multi-modal therapy for muscle-invasive bladder cancer could benefit patients by enhancing the anti-tumor activity of standard of care chemotherapy. It allowed for dose reduction of cisplatin and increased the efficacy of carboplatin. This may allow more patients currently unfit for cisplatin-based therapy to benefit from treatment.

Keywords

urothelial carcinoma

muscle-invasive bladder cancer

metastatic bladder cancer

cisplatin

carboplatin

References

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