Tripeptide tyroserleutide plus doxorubicin: therapeutic synergy and side effect attenuation

Nude mice bearing human hepatocellular carcinoma BEL-7402 tumors were treated with successive intraperitoneal injections of saline; low-, mid-, or high-dose doxorubicin; or low-, mid-, or high-dose doxorubicin plus YSL. Effects on the weight and volume of the tumors were evaluated.Co-administration of YSL and high-dose doxorubicin (6 mg/kg every other day) prolonged the survival time of tumor-bearing mice as compared to high-dose doxorubicin alone. As well, the anti-tumor effects of mid- and low-dose doxorubicin (2 and 0.7 mg/kg every other day, respectively) were enhanced when supplemented with YSL; the tumor growth inhibition rates for YSL plus doxorubicin were greater than the inhibition rates for the same dosages of doxorubicin alone. The combination of YSL and doxorubicin decreased chemotherapy-associated weight loss, leukocyte depression, and heart, liver, and kidney damage as compared to doxorubicin alone.The combination of YSL plus doxorubicin enhances the anti-tumor effect and reduces the side effects associated with doxorubicin chemotherapy.According to the World Health Organization, 7.6 million people succumbed to cancer in 2005, accounting for 13% of all deaths. However, in China, the cancer death rate was 20.2%, and it is expected to reach 23.6% by 2023. Liver cancer is the third most common cause of death in China [1].Anthracene-nucleus antibiotics are anti-tumor drugs that have been heavily researched and developed for the past twenty years. Among those, doxorubicin is the most commonly used and the most important; however, its use has been increasingly limited due to severe associated side effects, such as myocardial toxicity and bone marrow depression [2]. Because the dosage of doxorubicin can be decreased when doxorubicin is given combination with other anti-tumor drugs, which can also elevate the therapeutic effect and relieve side effects of doxorubicin, combination therapy has become a common strategy for doxorubicin-based chemotherapy.Tripeptid