Previous report showed that
leukemia cells' differentiation could be induced by
retinoic acid (RA), and
prostate cancer cells' proliferation could be inhibited by
Vitamin D or its analog. This study aimed to examine whether RA and
vitamin D analog
EB1089 have synergistic effect on
hepatocellular cancer cells' apoptosis. The
hepatocellular cancer cell lines' viability was determined by MTT method after treating by RA and
EB1089 alone or in combination, cell cycle of SSMC-7721 cell analyzed by FACS, mitochondrial membrane potential of SSMC-7721 under different treatments were detected using
MitoTracker Red CMXRos. TUNEL analysis was also used for cell apoptosis detection. Real time-PCR and Western Blot assay were used to detect the expression of Bcl-2 and Bax. Moreover,
hepatocellular cancer model was developed by subcutaneously (S.C.) challenging H22 cells to nude mice. In the combination group (10 μmol/L RA, 10 nmol/L
EB1089), the viability of
hepatocellular cancer cells decreased significantly compared with drugs used alone (P < 0.05). From the TUNEL analysis, SSMC-7721 cells have a higher apoptotic ratio in the combined
drug group than in the groups for which the drugs were used separately. In a
hepatocellular cancer model, the
tumor weight of H22
tumor bearing mice was more reduced in the combined
drug treated group when compared to the groups for which the drugs were used alone (P < 0.05), in addition, significantly prolonged survival was observed. Combination of RA and
EB1089 exert synergistic growth inhibition and apoptosis induction on
hepatocellular cancers cells.