Knockdown of NANOG enhances chemosensitivity of liver cancer cells to doxorubicin by reducing MDR1 expression.

Abstract

Multidrug resistance (MDR) is one of the major reasons for the failure of liver cancer chemotherapy, and its suppression may increase the efficacy of chemotherapy. NANOG plays a key role in the regulation of embryonic stem cell self-renewal and pluripotency. Recent studies reported that NANOG was abnormally expressed in several types of tumors, indicating that NANOG is related to tumor development. However, the correlation between NANOG and liver cancer chemoresistance remains uncertain. In this study, RNA interfere technology was employed to knock down NANOG expression in HepG2 human liver cancer cells. We found that the knockdown of NANOG expression in NANOG siRNA-transfected HepG2 cells resulted in decreased colony formation rate and cell migration compared to control HepG2 cells. In addition, HepG2 cells were treated with doxorubicin to evaluate the chemosensitivity to doxorubicin. We found that the doxorubicin sensitivity of HepG2 cells was increased with downregulation of NANOG expression. The expression of MDR1 at both mRNA and protein levels was decreased in HepG2 cells when NANOG was knocked down. These findings suggest that the knockdown of NANOG in HepG2 human cells resulted in decreased MDR1 expression and increased doxorubicin sensitivity, and NANOG could be used as a novel potential therapeutic target to reverse multidrug resistance of liver cancer.

• Authors: Jia-Jia Zhou, Xiao-Geng Deng, Xiao-Yu He, Yu Zhou, Min Yu, Wen-Chao Gao, Bing Zeng, Quan-Bo Zhou, Zhi-Hua Li, Ru-Fu Chen
• Journal: International journal of oncology (Int J Oncol) Vol. 44 Issue 6 Pg. 2034-40 (Jun 2014) ISSN: 1791-2423 [Electronic] Greece
• PMID: 24647772 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• Antineoplastic Agents
• Homeodomain Proteins
• NANOG protein, human
• Nanog Homeobox Protein
• Doxorubicin

Topics

• ATP Binding Cassette Transporter, Subfamily B (genetics, metabolism)
• Antineoplastic Agents (pharmacology)
• Cell Movement
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm (drug effects, genetics)
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Hep G2 Cells
• Homeodomain Proteins (genetics, metabolism)
• Humans
• Liver Neoplasms (drug therapy, genetics, pathology)
• Nanog Homeobox Protein