Effectiveness of local injection of lentivirus-delivered stathmin1 and stathmin1 shRNA in human gastric cancer xenograft mouse.
OBJECTIVE
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 shRNA 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. STMN1 shRNA group (n = 6) were given local injection of lentivirus-delivered STMN1 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 mRNA and protein level, respectively.


RESULTS
Experimental therapy on the nude mice model bearing subcutaneous tumor of SGC-7901 cells showed that local administration of STMN1 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 STMN1-treated group as compared with non-silencing shRNA group (P < 0.05). Quantitative reverse transcription-polymerase chain reaction and Western blot showed downregulation of STMN1 gene expression in STMN1 shRNA group as compared with non-silencing shRNA group (P < 0.05).


CONCLUSIONS
These findings highlight the potential use of local injection of lentivirus-delivered shRNA for the treatment of early localized human gastric carcinoma.
Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
Javed
J
Akhtar
Zhou
Z
Wang
Che
C
Yu
Zhi Ping
ZP
Zhang
D000818:Animals; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use*; D064593:Heterografts; D006801:Humans; D015552:Injections, Intralesional; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D050777:Stathmin / Q000008:administration & dosage* / Q000235:genetics*; D013274:Stomach Neoplasms / Q000628:therapy*
D034741:RNA, Small Interfering; C493995:STMN1 protein, human; D050777:Stathmin
RNA interference; gastric cancer; lentivirus; posttranscriptional gene silencing (PTGS); shRNA; stathmin; tumor xenograft model