Dexamethasone decreases hepatocellular carcinoma cell sensitivity to cisplatin-induced apoptosis.

Abstract

BACKGROUND/AIMS:

Despite the fact that dexamethasone (DEX), a synthesized glucocorticoid (GCs), in vitro has pro-apoptotic effects on lymphoid cells, it has been suggested to induce apoptosis resistance toward chemotherapy in lung, cervical and breast cancer cell lines. However, the mechanisms by which GCs inhibit apoptosis in some cells have not been elucidated. The aim of this study is to investigate the effect of DEX on cisplatin (CIS)-induced hepatocellular carcinoma cell proliferation, apoptosis and to determine apoptosis-related gene expression on mRNA and protein levels.

METHODOLOGY:

MTT assay, annexin V-FITC as well as Hoechst33258 staining were performed to detect hepatocellular carcinoma cell proliferation and apoptosis, respectively. RT-PCR and western blot were used to determine Bcl-2 and Bcl-xL expression.

RESULTS:

DEX alone did not cause any obvious change to HepG2 and SNU449 cell proliferation. When pretreated with DEX followed by CIS treatment, cells showed resistance to CIS-induced cytotoxicity by MTT assay and apoptosis detected by Annexin V-FITC kit double staining. Hoechst33258 staining showed that CIS caused cell nuclear condensation, a sign of apoptosis and DEX pretreatment reduced the proportion of apoptotic cells. Anti-apoptotic genes Bcl-2 and Bcl-xL expression levels decreased after CIS treatment, but increased again after DEX addition.

CONCLUSIONS:

DEX can decrease hepatocellular carcinoma cell sensitivity to CIS-induced cell death by preventing cell apoptosis.

• Authors: Ning Yang, Haibin Zhang, Hui Si-Ma, Yong Fu, Wenchao Zhao, Dongyu Li, Guangshun Yang
• Journal: Hepato-gastroenterology (Hepatogastroenterology) 2011 Sep-Oct Vol. 58 Issue 110-111 Pg. 1730-5 ISSN: 0172-6390 [Print] Greece
• PMID: 21940343 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Antineoplastic Agents, Hormonal
• Proto-Oncogene Proteins c-bcl-2
• bcl-X Protein
• Dexamethasone
• Cisplatin

Topics

• Antineoplastic Agents (pharmacology)
• Antineoplastic Agents, Hormonal (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Carcinoma, Hepatocellular (drug therapy, genetics)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cisplatin (pharmacology)
• Dexamethasone (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Liver Neoplasms (drug therapy, genetics)
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• Staining and Labeling
• Tumor Cells, Cultured
• bcl-X Protein (genetics)