Octamer 4 (Oct4) mediates chemotherapeutic drug resistance in liver cancer cells through a potential Oct4–AKT–ATP‐binding cassette G2 pathway†

• DOI: 10.1002/hep.23692
• Publication Date: 2010-03-26T19:03:36Z
• Authors: Xiao Qi Wang; Weg M. Ongkeko; Lin Chen; Zhen Fan Yang; Ping Lu; Kwok Kin Chen; Jay P. Lopez; Ronnie T.P. Poon; Sheung Tat Fan
• Keywords: 0303 health sciences; Neoplasm - physiology; Carcinoma, Hepatocellular; Hepatocellular - drug therapy; Carcinoma; Liver Neoplasms; Drug Resistance; ATP-Binding Cassette Transporters - physiology; 3. Good health; Octamer Transcription Factor-3 - physiology; Oncogene Protein v-akt; 03 medical and health sciences; Drug Resistance, Neoplasm; Tumor Cells, Cultured; Humans; ATP-Binding Cassette Transporters; Drug Resistance, Neoplasm - physiology; Liver Neoplasms - drug therapy; Octamer Transcription Factor-3; Carcinoma, Hepatocellular - drug therapy; Signal Transduction

Chemoresistance presents a major obstacle to the efficacy of chemotherapeutic treatment cancers. Using drugs select drug-resistant cancer cells in hepatocellular carcinoma (HCC) and several other cell lines, we demonstrate that chemoresistant displayed stem features, such as increased self-renewal ability, motility, multiple drug resistance, tumorigenicity. Octamer 4 (Oct4) messenger RNA (mRNA) levels were dramatically due DNA demethylation regulation Oct4. By functional study, Oct4 overexpression enhanced whereas knockdown reduced liver resistance vitro xenograft tumors. It is known Oct4-TCL1-AKT pathway acts on embryonic proliferation through inhibition apoptosis. We further induced activation TCL1, AKT, ABCG2 mediate chemoresistance, which can be overcome by addition PI3K/AKT inhibitor; therefore, direct Oct4-TCL1-AKT-ABCG2 or combination with AKT-ABCG2 could potential new mechanism involved chemoresistance. Moreover, clinical significance Oct4-AKT-ABCG2 demonstrated HCC patients, strong correlation expression patterns human The role axis machinery suggests AKT (PI3K inhibitors) not only inhibits proliferation, but may also enhance chemosensitivity target cells. Conclusion: Oct4, transcriptional factor pluripotent cells, chemoresistance pathway. (HEPATOLOGY 2010;)