Efficacy of treatment with siRNA targeting Bcl-2 in combination with HCPT against transplanted H₂₂ hepatoma in mice.
- Author:
Hong-hua HU
1
;
Hai-xing SONG
2
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Antineoplastic Agents, Phytogenic; pharmacology; Apoptosis; drug effects; Camptothecin; analogs & derivatives; pharmacology; Cell Cycle; drug effects; Drug Synergism; Liver Neoplasms, Experimental; metabolism; pathology; Male; Mice; Mice, Inbred BALB C; Proto-Oncogene Proteins c-bcl-2; genetics; metabolism; RNA, Messenger; metabolism; RNA, Small Interfering; genetics; Random Allocation; Transfection; Tumor Burden; drug effects
- From: Chinese Journal of Oncology 2013;35(12):892-896
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the efficacy of treatment with siRNA targeting Bcl-2 in combination with HCPT against H₂₂ hepatoma transplanted in mice.
METHODSsiRNA targeting Bcl-2 mRNA was successfully designed and synthesized. Then, the Bcl-2 siRNA was transfected into H₂₂ hepatoma transplanted in mice in combination with HCPT for treatment. The changes of tumor volume, body weight and survival rate were observed. Tumor tissues were processed into paraffin blocks and sections were stained with hematoxylin and eosin (HE) to investigate the morphological changes of the tumor cells. RT-polymerase chain reaction (PT-PCR) was used to assess the expression of Bcl-2 mRNA in tumors and cells. Cell cycle and apoptosis of H₂₂ hepatoma cells transplanted in mice were further determined by flow cytometry.
RESULTSAfter treatment for 21 days, the tumor volume was around (571.47 ± 67.31)mm³ in the group of siRNA in combination with HCPT, which was significant smaller than that of the groups of HCPT [(880.47 ± 107.31) mm³, P < 0.05], siRNA interfere [(1119.55 ± 158.60)mm³, P < 0.01] and saline (1357.64 ± 197.92)mm³, P < 0.01]. The median survival time of the group receiving siRNA in combination with HCPT treatment was 26 days, which was significantly longer than that of the group receiving HCPT (14 day, P < 0.05), siRNA interfere (21 day, P < 0.05) and saline (12 day, P < 0.05). Larger necrotic area, lower expression of Bcl-2 mRNA, less cells at S phase and more apoptotic cells could be obviously seen in tumor tissues in the group of siRNA in combination with HCPT treatment.
CONCLUSIONBcl-2 siRNA in combination with HCPT has good synergetic antitumor efficacy in H₂₂ hepatoma-bearing mice.