Combined application of Doxorubicin and Naringin enhances the antitumor efficiency and attenuates the toxicity of Doxorubicin in HeLa cervical cancer cells.

The application of Doxorubicin (DOX) in the chemotherapy of cervical cancer is seriously hampered by the side effects of DOX, especially the cardiotoxicity and nephrotoxicity. Naringin (NIN), a bioflavonoid found in citrus fruit extract, has demonstrated a marked ability to inhibit preclinical models of cancer cell growth and tumor formation. Moreover, its other pharmacological effects are also widely explored. In this study, the antitumor activities of DOX, NIN and their combination were tested in vitro and in vivo. In addition, the attenuation of NIN toward DOX was also explored. Our data demonstrated that the combined application of DOX and NIN more effectively inhibited the cell proliferation than single agent in vitro. In the in vivo antitumor test, the combined application of DOX and NIN more effectively inhibited the growth of HeLa cervical tumor and promoted cell apoptosis. More importantly, the body weight loss and cardiotoxicity, nephrotoxicity and hepatotoxicity were obviously attenuated compared to the DOX treatment group. Taken together, all the results indicated that the combined application of DOX and NIN could inhibit the growth of HeLa cervical cancer cells and attenuate the toxicity of DOX, which suggested NIN could be used as a combined agent for the prevention and treatment of cervical cancer.