| Objective: To investigate the effects of 1α,25-dihydroxyvitamin D3 (1,25D3) and all-trans retinoic acid (ATRA) on growth and cell cycle in hepatoma HepG2 cells and colon cancer LoVo cells, and its molecular mechanism.Methods: After HepG2 cells and LoVo cells were treated with 1,25D3, ATRA or combination of both, survival and morphological changes were determined by MTT assay and light microscope, cell cycle and apoptosis were determined by flow cytometry (FCM) and dual staining of AnnexinV/PI, and the mRNA and protein expression of P21WAF/CIP1 and P27KIP1 were determined by RT-PCR and FCM.Results: 1,25D3 or ATRA alone or combination of both inhibited the growth of HepG2 cells and LoVo cells in a time- and dose-dependent manner. The inhibition was more obvious in the combination group than the group alone (P<0.05). FCM analysis indicated that combination of 1,25D3 and ATRA induced more strongly G1 phase arrest than alone of HepG2 cells and LoVo cells. All of them could induce apoptosis (P<0.05). The RT-PCR results showed that the mRNA expression of p21WAF/CIP1 not p27KIP1 were higher in the cells treated with 1,25D3 or 1,25D3 combined with ATRA than the control after 24 hour treatment. FCM showed that the combination of 1,25D3 and ATRA markedly enhanced the expression of p21WAF/CIP1 and p27KIP1 in protein level as compared with 1,25D3 alone.Conclusion: 1,25D3 and ATRA could induce growth inhibition and apoptosis of HepG2 cells and LoVo cells, and the molecular basis of the cell cycle blockade by 1,25D3 may be associated with the expression of CDK inhibitors (p21WAF/CIP1 and p27KIP1) in HepG2 cells, which mediate a G1 arrest. Furthermore, the combination of 1,25D3 and ATRA can exert synergistically inhibitory effect on the growth of HepG2 cells and LoVo cells.
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