J Cancer 2020; 11(13):3955-3964. doi:10.7150/jca.41783

Research Paper

Synergistic Effects of Curcumin and 5-Fluorouracil on the Hepatocellular Carcinoma In vivo and vitro through regulating the expression of COX-2 and NF-κB

Ting Xu1#, Pu Guo1#, Chao Pi1#, Yingmeng He1, Hongru Yang2,3, Yi Hou1, Xianhu Feng1, Qingsheng Jiang4, Yumeng Wei1✉, Ling Zhao1✉

1. Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, No. 319, Zhongshan Rd Sanduan, Jiangyang District,Luzhou, Sichuan, 646000, P.R.China
2. The Affiliated Hospital, Southwest Medical University, No.25, Taiping Street, Luzhou, Sichuan, 646000, China
3. Department of Oncology, Luzhou People's Hospital, No.316, Jiugu Dadao Erduan, Luzhou, Sichuan, 646000, China
4. School of International Education, Southwest Medical University, No.1, Xianglin Rd Yiduan, Longmatan District, Luzhou, Sichuan, 646000, China
#These authors contributed equally to this work.

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Citation:
Xu T, Guo P, Pi C, He Y, Yang H, Hou Y, Feng X, Jiang Q, Wei Y, Zhao L. Synergistic Effects of Curcumin and 5-Fluorouracil on the Hepatocellular Carcinoma In vivo and vitro through regulating the expression of COX-2 and NF-κB. J Cancer 2020; 11(13):3955-3964. doi:10.7150/jca.41783. Available from https://www.jcancer.org/v11p3955.htm

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Abstract

Curcumin (CU) has shown broad anti-cancer effects. 5-fluorouracil (5-FU) has been a conventional chemotherapeutic agent for hepatocellular carcinoma. Unfortunately, the nonspecific cytotoxicity and multidrug resistance caused by long-term use limited the clinical efficacy of 5-FU. This study was aimed to investigate whether the combination of CU and 5-FU could generate synergistic effect in inhibiting the human hepatocellular carcinoma. The results of cytotoxicity test showed that compared with applying single drugs, the combination of CU and 5-FU (1:1, 1:2, 1:4, 2:1 and 4:1, mol/mol) presented stronger cytotoxicity in SMMC-7721, Bel-7402, HepG-2 and MHCC97H cells, while the combination groups are relatively insensitive to normal hepatocytes (L02). Among them, the molar ratio of 2:1 combination group showed strong synergistic effect in SMMC-7721cells. Then, western blotting assay further verified that the mechanism of the synergistic effect may be related to the inhibition of the expression of NF-κB (overall) and COX-2 protein. In addition, the synergistic effect was also validated in the xenograft mice in vivo. This research not only provides a novel and effective combination strategy for the therapy of hepatocellular carcinoma but also provides an experimental basis for the development of CU and 5-FU compound preparation.

Keywords: Curcumin, 5-Fluorouracil, Hepatocellular carcinoma cell lines, COX-2, NF-κB