| Objective:To investigate the effect of SAHA on the radiosensitization and proliferation of pancreatic cancer cell line
Patu8988.Methods:Different concentrations (0, 0.5, 1, 2, 4, 6, 8 umoL/L) of SAHA were treated in human pancreatic cancer cell line
Patu8988 for 12, 24, 36 and 48 h, the growth inhibition was detected by MTT colorimetric assay, and the effect of IC50 was calculated.
The blank control group and SAHA treatment group (20%IC50 SAHA 24 h) were set and treated by 6MV-X (0, 2, 4, 6, 8Gy) irradiation,
clone formation radiosensitizing effect on Patu8988 cells was examined by SAHA assay, multi-target click model fitting cell survival
curve, radiation related parameters of D0, Dq the value and radiosensitization ratio were calculated. Western Blot was used to detect the
effects of different concentrations (0, 4, 8, 12 umoL/L) of SAHA on the level of histone H4 acetylation, Ku70 and Bax protein expression
in Patu8988 cells.Results:SAHA could inhibit the proliferation of Patu8988 cells in a concentration and time dependent, the IC50 of 48h
was 5.40 滋mol/L. The colony formation rate of SAHA cells treated with Patu8988 combined with radiotherapy was significantly lower
than that of radiotherapy alone. The D0 was 1.513, 2.229, Dq were 0.783 and 1.321, respectively, and the radiation enhancement ratio
(SER) was 1.47. SAHA could increase the level of histone H4 acetylation in Patu8988 cells, inhibit the expression of DNA repair protein
Ku70, and promote the expression of apoptosis related genes Bax in a dose-dependent manner (P<0.05).Conclusion:SAHA could inhibit
the proliferation of pancreatic cancer Patu8988 cells in a concentration and time-dependent manner and had radiosensitizing effect, it
might be related to the inhibition of DNA double strand repair and promotion of apoptosis. |
