Activating transcription factor 4 increases chemotherapeutics resistance of human hepatocellular carcinoma
| Autor: | Ning Liang, Chunyan Zhang, Chenghu Liu, Antao Chang, Yanhua Liu, Zongjin Li, Nan Bai, Jing Yin, Na Li, Dan Lv, Rong Xiang, Yaping Tian, Zhuhong Zhang, Xiaoyue Tan |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Carcinoma Hepatocellular Molecular Sequence Data Antineoplastic Agents Mice SCID Activating Transcription Factor 4 Biology Mice Reference Values In vivo Cell Line Tumor medicine Carcinoma Animals Humans neoplasms Pharmacology Cisplatin Gene knockdown Base Sequence Liver Neoplasms ATF4 medicine.disease Glutathione Xenograft Model Antitumor Assays digestive system diseases Liver Oncology Drug Resistance Neoplasm Apoptosis Gene Knockdown Techniques Hepatocellular carcinoma Cancer research Molecular Medicine medicine.drug |
| Zdroj: | Cancer Biology & Therapy. 13:435-442 |
| ISSN: | 1555-8576 1538-4047 |
| Popis: | It has been reported that activating transcription factor 4 (ATF4) increases the processes of tumor growth, metastasis and drug resistance. However, the role played by ATF4 in chemoresistance of hepatocellular carcinoma (HCC) remains unknown. Clarification of this role of ATF4 in HCC could greatly benefit the efficacy of clinical treatment of HCC. In this study, we found that ATF4 was overexpressed in about 50.7% of HCC tissues. In fact knockdown of ATF4 significantly increased the cytotoxicity of cisplatin in both in vitro and in vivo assays, while overexpression of this molecule dramatically decreased the sensitivity of HCC cell lines to cisplatin. Additionally, we found that synthesis of glutathione was significantly reduced in HCC cell lines subjected to ATF4 knockdown. Taken together, these results demonstrate that ATF4 can increase resistance to cisplatin in HCC by increased biosynthesis of glutathione, and that this may be a potent novel target for the future development of anti-HCC drugs. |
| Databáze: | OpenAIRE |
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