Lentiviral-mediated RNA interference targeting stathmin1 gene in human gastric cancer cells inhibits proliferation in vi
- PDF / 876,955 Bytes
- 9 Pages / 595.28 x 793.7 pts Page_size
- 27 Downloads / 182 Views
RESEARCH
Open Access
Lentiviral-mediated RNA interference targeting stathmin1 gene in human gastric cancer cells inhibits proliferation in vitro and tumor growth in vivo Javed Akhtar, Zhou Wang*, Zhi Ping Zhang and Ming Ming Bi
Abstract Background: Gastric cancer is highly aggressive disease. Despite advances in diagnosis and therapy, the prognosis is still poor. Various genetic and molecular alterations are found in gastric cancer that underlies the malignant transformation of gastric mucosa during the multistep process of gastric cancer pathogenesis. The detailed mechanism of the gastric cancer development remains uncertain. In present study we investigated the potential role of stathmin1 gene in gastric cancer tumorigenesis and examined the usefulness of RNA interference (RNAi) targeting stathmin1 as a form of gastric cancer treatment. Methods: A lentiviral vector encoding a short hairpin RNA (shRNA) targeted against stathmin1 was constructed and transfected into the packaging cells HEK 293 T and the viral supernatant was collected to transfect MKN-45 cells. The transwell chemotaxis assay and the CCK-8 assay were used to measure migration and proliferation of tumor cells, respectively. Quantitative real-time PCR and western blotting were used to detect the expression levels of stathmin1. Results: Lentivirus mediated RNAi effectively reduced stathmin1 expression in gastric cells. Significant decreases in stathmin1 mRNA and protein expression were detected in gastric cells carrying lentiviral stathmin-shRNA vector and also significantly inhibited the proliferation, migration in gastric cancer cells and tumorigenicity in Xenograft Animal Models. Conclusions: Our findings suggest that stathmin1 overexpression is common in gastric cancer and may play a role in its pathogenesis. Lentivirus mediated RNAi effectively reduced stathmin1 expression in gastric cells. In summary, shRNA targeting of stathmin1 can effectively inhibits human gastric cancer cell growth in vivo and may be a potential therapeutic strategy for gastric cancer. Keywords: Stathmin1, Gastric cancer, Lentivirus, shRNA
Background Gastric cancer is one of the most common cancers worldwide with approximately 989,600 new cases and 738,000 deaths per year, accounting for about 8 percent of new cancers [1]. The worldwide incidence of gastric cancer has declined rapidly over the recent few decades. Despite its recent decline, gastric cancer is the fourth
* Correspondence: [email protected] Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, 250021, Shandong, China
most common cancer and the second leading cause of cancer-related death worldwide [2,3]. It has the highest incidence in China, Japan, Iran, Korea and eastern Asia. The overall prognosis is poor with a 5-year survival rate below 30% in most countries [4]. In China, the decline was less dramatic than other countries; despite an overall decrease in gastric cancer incidence, an increase has been observed in the oldest and the youngest group, and a less remarka
Data Loading...
