title: Combination treatment with paclitaxel and doxorubicin inhibits growth of human esophageal squamous cancer cells by inactivation of Akt.
abstract: Despite the fact that paclitaxel and doxorubicin are widely used as chemotherapy agents against several types of cancer, their combined effects on esophageal squamous cell carcinoma (ESCC) have never been fully elucidated. The present study was designed to investigate the biological effects of paclitaxel and doxorubicin in ESCC cells. Combination treatment with paclitaxel and doxorubicin significantly inhibited the proliferation of TE-12 cells in a dose-and time-dependent manner compared to treatment with paclitaxel or doxorubicin alone. FACS analysis showed that the percentage of cells in the G2/M phase was significantly increased at 12 h after treatment with the combination. Increased p-cdc2, p-Wee1 and p53 protein levels were observed, while Akt activation was suppressed by combination treatment with paclitaxel and doxorubicin. In addition, treatment with paclitaxel plus doxorubicin significantly increased apoptosis as indicated by increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-7 and -9 levels. These results suggest that combination treatment with paclitaxel and doxorubicin induced G2/M cell cycle arrest and apoptosis in human ESCC cells by suppressing Akt activity. These findings highlight the potent apoptotic effect of combination therapy with paclitaxel and doxorubicin in ESCC cells and the potential clinical benefits of these two drugs in esophageal cancer.
authors.affiliation: Department of Physiology, Institute for Medical Sciences, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, Republic of Korea.
authors.forename: Hwan Hee
authors.initials: HH
authors.lastname: Lee
authors.forename: Shuai
authors.initials: S
authors.lastname: Ye
authors.forename: Xiu Juan
authors.initials: XJ
authors.lastname: Li
authors.forename: Kwang Bok
authors.initials: KB
authors.lastname: Lee
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Park
authors.forename: Soo Mi
authors.initials: SM
authors.lastname: Kim
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019926:Cyclin B / Q000096:biosynthesis; D018844:Cyclin-Dependent Kinases; D004317:Doxorubicin / Q000627:therapeutic use*; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D017239:Paclitaxel / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D019926:Cyclin B; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D053179:Caspase 7; D053453:Caspase 9; D017239:Paclitaxel