Fig. 4

CDK5 promotes apoptosis and oxaliplatin-mediated chemosensitivity in gastric cancer. (A) Annexin V/PI staining for apoptosis assessed the apoptosis rates in AGS and MKN45 cells after reconstitution of CDK5. The quantification of apoptosis rates is shown as the mean ± SD of 3 independent experiments (right); *p < 0.05 and **p < 0.01. (B–D) Western blots of CDK5, total/cleaved poly-(ADP-ribose) polymerase (PARP), and total/cleaved caspase 3 in AGS and MKN45 cells. Panel B shows that the cells were transfected with the indicated amounts (0.25, 0.5 or 1.0 µg) of pLV-CDK5 expression plasmid or empty vector (CTRL). Panel C shows that the cells were treated with the indicated amounts (0.25, 0.5 or 1.0 µM) of oxaliplatin (OXA) or DMSO (CTRL). Panel D shows that the cells were treated with 0.5 µM OXA or siRNA targeting CDK5. (E) Cell viability assay results show the IC50 curves for oxaliplatin in the AGS and MKN45 cell lines with CDK5 overexpression. (F) Gross morphology of tumors in nude mice using MKN45 cells with CDK5 overexpression or combined with OXA treatment. The mice were dosed with OXA (2 mg/kg, intraperitoneally) (n = 5 tumors per group). (G) Tumor growth curve over time for each group. Data are shown as the mean ± SEM. (H) Relative tumor volume at the end of treatment. Lines in the graph indicate the median of tumor volume. **p < 0.01, ***p < 0.001, and ****p < 0.0001. (I) Western blots of CDK5, total/cleaved PARP, and total/cleaved caspase 3 from xenograft tumors