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.

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.

Application of curcumin and its derivatives in tumor multidrug resistance.

Malignant tumor endangers seriously the health of all mankind. Multidrug resistance (MDR) is one of the main causes of clinical tumor chemotherapy failure. Curcumin (CUR) has not only antitumor activity but also reversing tumor MDR effect. CUR reverses tumor MDR via regulating related signal pathways or corresponding expressed proteins or gene. When combined with chemotherapeutic agents, CUR can be a chemotherapeutic sensitive agent to enhance chemotherapy efficacy and weaken tumor MDR. On the other hand, to improve the MDR reversal effect of CUR, its derivatives have been extensively studied. Therefore, this article mainly focuses on reviewing the application of CUR and its derivatives in MDR and its mechanism of reversing MDR.

Co-delivery system of chemotherapy drugs and active ingredients from natural plants: a brief overview of preclinical research for cancer treatment.

Introduction: Many active ingredients from natural plants (AINPs) have been revealed to possess remarkable anticancer properties. Combination chemotherapy of chemo-drugs and AINPs has also proven to be more advantageous than individual chemo-drug treatment with respect to enhancing efficiency, alleviating toxicity, and controlling the development of multidrug resistance (MDR). Co-delivery is considered a promising method to effectively achieve and manage combination chemotherapy of chemo-drugs and AINPs, and various distinctive and functional co-delivery systems have been designed for these purposes to date.Areas covered: This review focuses on recent preclinical investigations of co-delivery systems for chemo-drugs and AINPs as new cancer treatment modalities. We particularly emphasize the apparent treatment advantages of these approaches, including augmenting efficiency, reducing toxicity, and controlling MDR.Expert opinion: There has already been notable progress in the application of combination chemotherapy with co-delivery systems loaded with chemo-drugs and AINPs based on results with cellular and animal models. The main challenge is to translate these successes into new anticancer compound preparations and promote their clinical application in practice. Nevertheless, continuous efforts with new designs of co-delivery systems remain essential, providing a foundation for future clinical research and development of new anticancer drugs.