Black raspberry anthocyanins increased the antiproliferative effects of 5-Fluorouracil and Celecoxib in colorectal cancer cells and mouse model

Abstract

With long-term use of chemotherapy drugs, the effect of chemotherapy decreased significantly. Therefore, it is important to find a strategy to improve the efficacy of chemotherapy drugs. Our previous studies have found that black raspberry (BRB) anthocyanins exhibit chemoprevention function in colorectal cancer (CRC). Herein, we found that BRB anthocyanins combined with 5-Fluorouracil or Celecoxib could enhance their chemotherapy efficiency. Combinational use of BRB anthocyanins with 5-Fluorouracil or Celecoxib could inhibit the CRC cell proliferation in vitro, and decrease the number of tumors in AOM-induced CRC mice in vivo. Mechanism studies found increased level of tumor suppressor PTEN, reduced expression of EZH2 and followed inhibition on AKT signaling pathway and reversed expression of drug resistance gene MDR1 might play important roles in synergistic effect using BRB anthocyanins with 5-Fluorouracil or Celecoxib. Current data may provide a new treatment strategy for CRC by using BRB anthocyanins as adjunct with chemotherapy drugs.

Keywords

• Black raspberry anthocyanins
• EZH2
• Colorectal cancer
• Chemotherapy drugs
• Synergistic effect