title: Molecular mechanism of inhibitory effects of C-phycocyanin combined with all-trans-retinoic acid on the growth of HeLa cells in vitro.
abstract: We studied the effects of all-trans-retinoic acid (ATRA), C-phycocyanin (C-PC), or ATRA+C-PC on the growth of cervical cells (HeLa cells), cell cycle distribution, and apoptosis. The anticancer mechanism of the drug combination was revealed. MTT assay was adopted to determine the effects of C-PC and ATRA on the growth of HeLa cells. The expression quantities of cyclin-dependent kinase (CDK) 4, cyclin D1, Bcl-2, caspase-3, and CD59 were determined by in situ hybridization, immunofluorescence, immunohistochemistry staining, Western blot, and RT-PCR. TUNEL assay was adopted to determine the cellular apoptosis levels. Both C-PC and ATRA could inhibit the growth of HeLa cells, and the combination of ATRA+C-PC functioned cooperatively to induce apoptosis in HeLa cells. The dosage of ATRA was reduced when it cooperated with C-PC to reduce the toxicity. ATRA treated with C-PC could induce more cell cycle arrests than the single drug used by decrease in cyclin D1 and CDK4 expression. The combination of the two drugs could upregulate caspase-3 and downregulate the Bcl-2 gene and induce cell apoptosis. Moreover, the combination therapy has an important immunological significance in decreased expression of the CD59 protein. Singly, C-PC or ATRA could inhibit the growth of HeLa cells, and the effects of treatment were further enhanced in the combination group. In combination with C-PC, the dosage of ATRA was effectively reduced. The C-PC + ATRA combination might take effect by inhibiting the progress of the cell cycle, inducing cell apoptosis and promoting complement-mediated cytolysis.
authors.affiliation: Department of Biology, Medical College of Qingdao University, 38 Dengzhou Road, Qingdao, 266021, People's Republic of China, 851902313@qq.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Chu
authors.forename: Cong-Yi
authors.initials: CY
authors.lastname: Lv
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Xu
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D018957:CD59 Antigens / Q000032:analysis; D053148:Caspase 3 / Q000032:analysis; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000032:analysis; D051358:Cyclin-Dependent Kinase 4 / Q000032:analysis; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D010798:Phycocyanin / Q000008:administration & dosage*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D014212:Tretinoin / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D018957:CD59 Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; C051590:CD59 protein, human; D010798:Phycocyanin; D019938:Cyclin D1; D014212:Tretinoin; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D053148:Caspase 3