Overexpression of long non-coding RNA GHET1 promotes the development of multidrug resistance in gastric cancer cells.

Abstract

BACKGROUND AND AMID:

Multidrug resistance (MDR) is the main obstacle to successful chemotherapy for patients with gastric cancer (GC). The GHET1 affects a variety of cancer development, and increased GHET1 promotes gastric carcinoma cell proliferation. This study amid to investigate the effect of GHET1 on the development of MDR in gastric cancer cells.

METHODS AND RESULTS:

In this study, we observed an increased expression levels of GHET1 in drug-resistant gastric cancer patients and cisplatin-resistant gastric cancer cell lines (BGC823/DPP and SGC7901/DDP cell line). Next, the two cell lines were used to in vitro validation of the effect of GHET1 expression on the MDR development. Silence of GHET1 in the two cisplatin-resistant gastric cancer cell lines inhibited the MDR with rising inhibition rate tested by MTT (methyl thiazolyl tetrazolium) assay. The apoptotic cell rate was analyzed by staining with Annexin V/PI. The results showed that the IC50 (half maximal inhibitory concentration) of the two cisplatin-resistant gastric cancer cell lines transfected with si-GHET1 were significantly reduced. Contrary to inhibition of GHET1 in the two cisplatin-resistant gastric cancer cell lines, we found that overexpression of GHET1 reduced sensitivity of BGC823 and SGC7901 cells to cisplatin with decreased inhibition rate and apoptotic cell rate and increased IC50. Furthermore, the qRT-PCR and western blot results showed that overexpression of GHET1 downregulated Bax expression and upregulated Bcl-2, MDR1 and MRP1 expression in BGC823 and SGC7901 cells.

CONCLUSION:

Highly expressing GHET1 promoted the development of MDR which was related to the Bax, Bcl-2, MDR1 and MRP1 genes expression in gastric cancer cells.

• Authors: Xianwen Zhang, Ping Bo, Liang Liu, Xizhi Zhang, Jun Li
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 92 Pg. 580-585 (Aug 2017) ISSN: 1950-6007 [Electronic] France
• PMID: 28578256 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• GHET1 transcript, human
• RNA, Long Noncoding
• Cisplatin

Topics

• Cell Line, Tumor
• Cisplatin (pharmacology)
• Dose-Response Relationship, Drug
• Drug Resistance, Multiple (drug effects, physiology)
• Drug Resistance, Neoplasm (drug effects, physiology)
• Gene Expression Regulation, Neoplastic
• Humans
• RNA, Long Noncoding (biosynthesis, genetics)
• Stomach Neoplasms (genetics, metabolism)