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

5-Fluorouracil (5-FU) or Celecoxib (Cel) combined with black raspberry anthocyanins enhanced the effect of chemotherapy drugs. Black raspberry anthocyanins increase the level of tumor suppressor PTEN by reducing the expression of EZH2, which inhibits the AKT signaling pathway and reverses the expression of a drugs resistance gene MDR1. [Display omitted] •BRB anthocyanins combined with 5-FU/Cel inhibited CRC cells proliferative.•BRB anthocyanins combined with 5-FU improved the tumorigenesis of CRC mice.•BRB anthocyanins synergistically enhanced 5-FU/Cel by EZH2/PTEN/AKT pathway. 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.