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Introduction
Incidence of hepatocellular carcinoma (HCC) ranks fifth among all malignant tumors. HCC is the second leading cause of cancer-associated mortality in the world. The overall 5-year survival rate of liver cancer is <5% (1). HCC is often accompanied by various degrees of cirrhosis, which accounted for between 70–90% of all cases in China in 2003 (2). As a result of cirrhosis, the patients with HCC have poor tolerance to drug therapy and have a high risk of surgical resection (3). Although tumor recurrence may be prevented by systemic and local chemotherapy to increase the postoperative survival rate, to a certain extent, following hepatectomy or liver transplantation, current chemotherapeutics have poor sensitivity and poor targeting and therapeutic effects (3). The severe systemic toxic effects and side effects result in functional damage of important organs, including the heart, liver and kidney (4). The causes limit the extensive application of current chemotherapeutics. HCC is drug resistant to the majority of chemotherapeutics, and the therapeutic effect is ~15% following systemic administration (2). Drug resistance may be overcome by increasing the effective drug concentration of tumor tissue, and the therapeutic effect can be increased (3,4). Brucine is a weak indole alkaloid with poor water solubility. It is one of the antitumor drugs that has been studied in recent years. The proliferation of human hepatoma SMMC-7721 cells was inhibited following the administration of brucine in vitro, which indicated that the inhibition rate increased as the drug concentration of brucine increased (5). At a brucine concentration of 320 µg/ml, the inhibition rate of cell proliferation was close to 100% (5). Deng et al (6–8) revealed that brucine was able to induce programmed cell death, caspase-9 proteolysis and mitochondrial membrane depolarization of HepG2 cells to kill liver cancer cells. Brucine was able to inhibit the tumor growth of mice with solid tumors, to a certain extent, and stimulate and facilitate the hematopoietic system and immune system, and restore the damage of liver and kidney function caused by Heps tumor inoculation (7). The results demonstrated that brucine was beneficial to the hematopoietic and immune systems of mice with solid tumors, and may be a novel and promising antitumor drug.
Brucine is limited in its clinical application for malignant tumors owing to its...