Inhibitory effect of E2F-1-silencing lentivirus vector on chemoresistance of subcutaneous human gastric cancer in nude mice.
- Author:
Fan-biao KONG
1
;
Xiao-tong WANG
;
Yu-bo XIE
;
Qiang XIAO
2
Author Information
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette, Sub-Family B, Member 1; genetics; metabolism; Animals; Antineoplastic Agents; pharmacology; Apoptosis; Cell Line, Tumor; Cisplatin; pharmacology; Drug Resistance, Neoplasm; E2F1 Transcription Factor; genetics; metabolism; Female; Gene Silencing; Genetic Vectors; Humans; Inhibitor of Apoptosis Proteins; genetics; metabolism; Lentivirus; genetics; Mice; Mice, Nude; Multidrug Resistance-Associated Proteins; genetics; metabolism; Neoplasm Transplantation; Proto-Oncogene Proteins c-myc; genetics; metabolism; RNA, Messenger; metabolism; Random Allocation; Repressor Proteins; genetics; metabolism; Stomach Neoplasms; genetics; metabolism; pathology; Transfection; Tumor Burden
- From: Chinese Journal of Oncology 2013;35(9):655-659
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the effects of E2F-1-silencing lentivirus vector on the growth and chemoresistance of subcutaneous human gastric cancer in nude mice.
METHODSThirty-six nude mice were inoculated subcutaneously with chemoresistant SGC-7901/DDP cells to establish subcutaneous tumor models of gastric carcinoma. The mice were randomly divided into E2F-1/RNAi-LV group, LV-scrRNAi group and PBS group (n = 12). E2F-1/RNAi-LV, LV-scrRNAi or PBS (0.1 ml per time) was injected into the mice, respectively, every two days. The nude mice received an intraperitoneal injection of cisplatin (25 mg/kg) every two days. The tumor volume was measured and histopathological changes of the tumors were observed by HE staining. The expressions of E2F-1, c-Myc, survivin, MDR1 and MRP were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Apoptosis in tumor xenografts was determined by in situ TUNEL labeling technique.
RESULTSThe mean tumor growth rate of the E2F-1/RNAi-LV group was significantly slower than that of the LV-scrRNAi and control groups (P < 0.05). The tumor volume of the E2F-1/RNAi-LV group was (745.13 ± 154.42)mm(3), significantly lower than that of the LV-scrRNAi and PBS groups (P < 0.05). Compared with that in the LV-scrRNAi and PBS groups, the expressions of mRNA and protein of E2F-1, c-Myc, survivin, MDR1 and MRP were significantly decreased in the E2F-1/RNAi-LV group (P < 0.05). The apoptotic rate in the E2F-1/RNAi-LV treatment group was (27.5 ± 9.7)%, significantly higher than (7.0 ± 1.1)% in the LV-scrRNAi group and (7.3 ± 1.2)% in the PBS group (P < 0.05).
CONCLUSIONIntra-tumoral injection of E2F-1/RNAi-LV shows significantly inhibitory effect on the tumor growth and chemoresistance of subcutaneous human gastric cancer in nude mice.
