Antitumor activity of alpha-fetoprotein conjugate with doxorubicin in vitro and in vivo

alpha-Fetoprotein (AFP) was conjugated with doxorubicin (DR) using glutaraldehyde as a cross-linking agent. The protein/DR molar ratio in the conjugate is 1 : 2. Cytotoxic activities (CTA) of the AFP-DR conjugate and of the free DR were compared using human mammary gland carcinoma cells, both DR-sensitive (MCF-7Wt) and DR-resistant (MCF-7AdrR). The CTA of the AFP-DR conjugate was fivefold higher than the CTA of the free DR for sensitive cells of the MCF-7Wt line and sevenfold higher for resistant cells of the MCF-7AdrR line. The CTA of the AFP-DR conjugate was also studied in vitro using the proliferating endothelium taken for a model of endothelial cell lining of blood vessels that supply the tumor. The AFP-DR conjugate was shown to have a high CTA for the endothelial cells (IC50 = 2.5 nM); thus, the conjugate is suggested to manifest an anti-angiogenic effect in vivo. The antitumor activity of the AFP-DR conjugate was studied using mice with inoculated melanoma B16 tumors. The treatment of animals significantly inhibited the tumor growth (>97%) and increased by 60% the mean life span of the animals compared to the control. The high antitumor efficiency of the AFP-DR conjugate and the possibility to significantly decrease the tumor cell resistance to DR make this conjugate a promising chemotherapeutic agent.