Molecular Mechanism Of Antineoplastic Of C-phycocyanin Combined With All-transretinoic

Objective We focused on studying the effects of all-transretinoic acid (ATRA), C-phycocyanin (C-PC) or ATRA+C-PC on the growth of tumor cells in vitro and in vivo. Furthermore, the anticancer mechanism of the drug combination was revealed.Methods MTT assay was adopted to determine the effects of C-PC and ATRA on the growth of HeLa and A549cells. The expression quantities of CDK-4, Cyclin D1, Bcl-2, caspase-3and CD59were determined by in situ hybridization, immunofluorescence, immunohistochemistry staining, Western blot and RT-PCR. TUNEL assay was used to determine the cellular apoptosis levels. The mice model with tumor were construct by subcutaneous injection of HeLa or A549cells into the left axilla of NU/NU mice. The weight of tumor and the spleen were tested. The activities of T-cells and spleen cells were determined by SRFC and MTT assay. TNF, Bcl-2and Cyclin Dl were determined by ELISA, immunohistochemistry staining and immunofluorescence.Results Both C-PC and ATRA could inhibit the growth of tumor cells in vivo and in vitro. The dosage of ATRA was reduced when it cooperated with C-PC so as to reduce the toxicity. The combination of ATRA+C-PC cooperatively functioned in the medium to high inhibition rate. ATRA+C-PC could decrease Cyclin D1, CDK-4and CD59expression, up-regulate caspase-3, down-regulate Bcl-2, and induce cell apoptosis. The single ATRA could inhibit the the activities of T-cells and spleen cells but the combination of the two drugs could further enhance this inhibitory effects. C-PC+ATRA could up-regulate TNF and down-regulate the expression of Bcl-2and Cyclin D1proteins in tumor.Conclusions C-PC+ATRA combination treatment possessed an efficient and low-toxic antitumor effect. C-PC+ATRA combination might take effects by inhibiting the progress of cell cycle, inducing cell apoptosis, promoting complement-mediated cytolysis and enhancing the immunity.