[Inducement effect of 9-cis retinoic acid on cell cycle arrest and apoptosis of gastric carcinoma cell line MGC803 and its mechanism].
OBJECTIVE
Antitumor effect of 9-cis retinoic acid (9-cis RA) on gastric carcinoma is unclear yet. This study was to explore the inducement effect of 9-cis RA on cell cycle arrest and apoptosis of gastric carcinoma cell line MGC803 and its mechanism.


METHODS
The expression of RXRalpha, Cyclin D1, and CDK4 in MGC803 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR). Cell cycle was detected by flow cytometry. The growth inhibition was analyzed by MTT assay. The apoptosis was detected by agarose gel electrophoresis and Hoechst33342/PI staining. The expression of apoptosis-associated gene Bcl-2 was detected by SP immunocytochemistry.


RESULTS
When treated with 0.1-10 micromol/L 9-cis RA for 96 h, the proliferation of MGC803 cells was significantly inhibited. The proportion of MGC803 cells at G1 phase was significantly increased when treated with 10 micromol/L 9-cis RA for 48, 72, and 96 h, and showed an apparent G1 phase arrest. When treated with 9-cis RA for 72 h, typical apoptotic changes, such as chromatin condensation and DNA ladder, were observed in MGC803 cells. The expression of Bcl-2 was significantly decreased in MGC803 cells when treated with 10 micromol/L 9-cis RA for 48 h. RXRalpha expression was at a low level in MGC803 cells and up-regulated when treated with 10 micromol/L 9-cis RA for 48 h (P<0.01). The expression of Cyclin D1 and CDK4 in MGC803 cells was both significantly down-regulated when treated with 10 micromol/L 9-cis RA for 96 h (P<0.01).


CONCLUSIONS
9-Cis RA could induce G1 phase arrest and apoptosis in MGC803 cells through down-regulating the expression of cell cycle factors Cyclin D1 and CDK4.
Xu
Rui-Cheng
RC
Department of Cellular Biology, Medical College of Chinese People's Armed Police Forces, Tianjin, 300162, P. R. China. Xu_rc@sohu.com
Zhou
Yan-Hong
YH
Hu
Wen-Liang
WL
D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D047490:Retinoid X Receptor alpha; D019938:Cyclin D1; D000077556:Alitretinoin; D014212:Tretinoin; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4