[Effects of retinoid Ro 40-8757 on human cancer cell lines in vitro].
OBJECTIVE
The retinoids are potent anti-tumor drugs affecting cellular proliferation and inducing cell differetiation or apoptosis. This study was designed to investigate the anti-proliferative effect of a new-developed retinoid, Ro 40-8757, on cell structure, cell cycle and cell cycle proteins of four human cancer cell lines in vitro in order to reveal its probable mechanism.


METHODS
MTT assay was used to determine the anti-proliferative effects of Ro 40-8757 on human cancer cell lines CCL-187, CCL-229, JF-305, and ASPC-1. Microscopy was used to observe CCL-187 morphological changes. Flow cytometry was performed to investigate the influence of Ro 40-8757 on cell cycle. Western blot analysis was conducted to detect the cell cycle proteins p16, p21, and p27 as to discuss the possible mechanism.


RESULTS
Ro 40-8757 significantly inhibited the growth of the four cancer cell lines in a dose-, time-dependent manner and without any signs of cytotoxicity, differentiation, or apoptosis. After treating with Ro 40-8757, the cell of CCL-187 was arrested at G0/G1 phase. Both p21 and p27 were rapidly increasing at the first 12 hours after exposed to the agent, then decreasing slowly in the 24, 48 hours, and increasing again in 72 to 144 hours. P16 did not express at all either before or after agent treatment.


CONCLUSIONS
The results suggest that Ro 40-8757 inhibits the growth of human cancer cell lines in vitro by means of cell cycle arrest (mediated by up-regulating cell cycle protein P21 and P27) instead of cytotoxic effects, differentiation, or apoptosis.
Lu
Jing
J
Key Lab of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110001, P. R. China.
Song
Jin-dan
JD
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009025:Morpholines / Q000494:pharmacology*; D012176:Retinoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D025521:Tumor Suppressor Proteins / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009025:Morpholines; D012176:Retinoids; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C081137:mofarotene