Inhibitory effect of resveratrol on the growth of human colon cancer ls174t cells and its subcutaneously transplanted tumor in nude mice and the mechanism of action.
- Author:
Jie CHEN
1
;
Xin-shu DONG
;
Xing-gang GUO
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Antineoplastic Agents, Phytogenic; pharmacology; Apoptosis; drug effects; Cell Cycle; drug effects; Cell Line, Tumor; Cell Proliferation; drug effects; Colonic Neoplasms; metabolism; pathology; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Proto-Oncogene Proteins c-bcl-2; genetics; metabolism; RNA, Messenger; metabolism; Stilbenes; pharmacology; Tumor Burden; drug effects; bcl-2-Associated X Protein; genetics; metabolism
- From: Chinese Journal of Oncology 2009;31(1):15-19
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the effect and mechanism of resveratrol against human colon cancer ls174t cells in vitro and the growth of colon cancer in tumor-bearing nude mice.
METHODSMTT method was used to test the inhibiting effect of resveratrol on the growth and proliferation of ls174t cells. Transmission electron microscopy was used to observe the morphological changes of cell apoptosis, and FCM assay was performed to measure the changes of cell apoptosis rate and cell cycle. RT-PCR method was used to detect the expression of bcl-2 and bax mRNA, and Western blot was used to detect the expression of bcl-2 and bax protein.
RESULTSMTT test revealed that resveratrol showed significant inhibiting effect on ls174t cells in a concentration- and time-dependent manner. In the concentration range of 25, 50, 100, 200 and 400 micromol/L, the inhibition rate after resveratrol treatment for 24 hours was respectively 1.0%, 9.1%, 17.4%, 27.8% and 66.5%, while the inhibition rate after treatment for 48 hours was respectively 3.6%, 13.7%, 30.2%, 58.4% and 86.1%, and the inhibition rate after treatment for 72 hours was 18.1%, 33.0%, 48.6%, 61.2% and 89.4%, respectively, showing a very significant difference (P < 0.01). Typical ultrastructural apoptotic changes were observed in resveratrol-treated ls174t cells. It was found through FCM assay that resveratrol caused apoptosis in ls174 cells and blocked the cell cycle at S phase. RT-PCR and Western blot test showed that after the treatment of colon cancer cells with resveratrol at different concentrations (25, 50, 100 and 200 micromol/L), the expression level of bcl-2 was decreased, while expression level of bax was increased. The highest inhibition rate was 47.9%. In 200 mg/kg and 800 mg/kg resveratrol treatment groups, the weight of subcutaneously transplanted tumors in nude mice was 4.10 +/- 0.18 g and 3.05 +/- 0.35 g, respectively, the difference was significant compared with that of the control group (P < 0.01).
CONCLUSIONResveratrol can inhibit the growth of ls174t cells through apoptosis induction. The mechanism is probably related to inhibition of anti-apoptotic factor bcl-2 and enhancement of expression of apoptotic factor bax.
