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Effectiveness of local injection of lentivirus‐delivered stathmin1 and stathmin1 shRNA in human gastric cancer xenograft mouse
Author(s) -
Akhtar Javed,
Wang Zhou,
Yu Che,
Zhang Zhi Ping
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12594
Subject(s) - small hairpin rna , gene silencing , gene knockdown , lentivirus , rna interference , medicine , cancer research , microbiology and biotechnology , cancer , apoptosis , biology , rna , immunology , gene , virus , biochemistry , viral disease
Background and Aim We have reported previously that RNA interference targeting stathmin1 (STMN1) gene in human gastric cancer cells inhibits proliferation in vitro and tumor growth in vivo . Based on these observations, in the present study, the possibility that local injection of lentivirus‐delivered stathmin sh RNA would induce regression of the established human gastric cancer xenograft in animal model was investigated. Methods BALB /c nude mice were inoculated subcutaneously into the right armpit with human gastric cancer cells SGC ‐7901 (2 × 10 6 cells in 200 μL phosphate‐buffered saline) to develop a xenograft model of human gastric cancer . When tumor reached suitable size, mice were randomly divided into two groups. STMN 1 shRNA group ( n = 6) were given local injection of lentivirus‐delivered STMN 1 shRNA , and the non‐silencing shRNA group ( n = 6) were administered with local injection of lentivirus‐delivered non‐silencing shRNA . Quantitative reverse transcription–polymerase chain reaction and Western blot were used to verify the knockdown of the gene expression in dissected tumor at m RNA and protein level, respectively. Results Experimental therapy on the nude mice model bearing subcutaneous tumor of SGC ‐7901 cells showed that local administration of STMN 1 shRNA effectively regressed the pre‐established tumors. Stathmin shRNA ‐treated tumors were significantly regressed as compared with that of the tumor injected with non‐silencing shRNA ( P < 0.05). Tumor weight was significantly decreased in STMN 1‐treated group as compared with non‐silencing shRNA group ( P < 0.05). Quantitative reverse transcription–polymerase chain reaction and Western blot showed downregulation of STMN 1 gene expression in STMN 1 shRNA group as compared with non‐silencing shRNA group ( P < 0.05). Conclusion These findings highlight the potential use of local injection of lentivirus‐delivered shRNA for the treatment of early localized human gastric carcinoma.