Leucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells

Overview

Journal Sci Rep

Specialty Science

Date 2017 Apr 8

PMID 28386133

Citations 13

Authors

Shu Wang

Lei Wang

Zhiyang Zhou

Qipan Deng

Ling Li

Mingzhi Zhang

Linlin Liu

Yong Li

Affiliations

Soon will be listed here.

Abstract

Colorectal cancer is a major cancer type worldwide. 5-fluorouracil, often given with leucovorin, is the most commonly used drug in colorectal cancer chemotherapy, yet development of drug resistance to 5-fluorouracil in colorectal cancer cells is the primary cause of chemotherapy failure. Most patients receiving intravenous 5-fluorouracil develop side effects. Leucovorin, due to its vitamin-like profile, has few side-effects. Drug repurposing is the application of approved drugs to treat new indications. In this study, we performed a novel drug-repurposing screening to identify Food and Drug Administration-approved chemotherapeutic compounds possessing synergistic activity with leucovorin against colorectal cancer cells. We found that the combination of bortezomib and leucovorin enhanced caspase activation and increased apoptosis in colorectal cancer cells better than either agent alone. Further, the synergistic induction of apoptosis and inhibition of tumor growth were also observed in mouse colorectal cancer xenografts. These data support leucovorin enhances the anti-cancer effect of bortezomib and present this novel combinatorial treatment against colorectal cancer.

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