DDX3 as a therapeutic target in colorectal cancer
sensitivity to RK-33 as the adherent cell lines (IC50 value range 3-9 µM). Treatment with RK-33 resulted in a G1 arrest in a dose-dependent manner in both HCT116 and HT29 (Figure 4F). An increase in the percentage of apoptotic cells could also be observed in HCT116 after DDX3 inhibition, but not in HT29 (supplementary Figure 1). The differences in cell cycle distribution were more profound than the increase in apoptotic cells, indicating that the primary effect of DDX3 inhibition is a G1 arrest, which ultimately can result in apoptosis.
4
Table 1. Clinicopathological characteristics of DDX3 low and DDX3 high colorectal cancers Total
Low DDX3
High DDX3
n
%
n
%
n
%
Total
303
100.0
179
59.1%
124
40.9%
Male
169
55.8%
102
57.0%
67
54.0%
Female
134
44.2%
77
43.0%
57
46.0%
1
22
9.6%
13
9.7%
9
9.4%
2
98
42.6%
54
40.3%
44
45.8%
3
80
34.8%
47
35.1%
33
34.4%
4
30
13.0%
20
14.9%
10
10.4%
well
16
5.3%
8
4.5%
8
6.5%
moderate
228
75.7%
134
75.3%
94
76.4%
poor
57
18.9%
36
20.2%
21
17.1%
Rectum
95
31.4%
56
31.3%
39
31.5%
Colon
208
68.6%
123
68.7%
85
68.5%
<40 mm
49
22.0%
24
19.0%
25
25.8%
40-60 mm
120
53.8%
69
54.8%
51
52.6%
>60 mm
54
24.2%
33
26.2%
21
21.6%
< 65 years
82
27.1%
54
30.2%
28
22.6%
65-80 years
167
55.1%
92
51.4%
75
60.5%
>80 years
54
17.8%
33
18.4%
21
16.9%
negative
230
99.1%
135
100.0%
95
97.9%
positive
2
0.9%
0
0.0%
2
2.1%
P-value
RR
95% CI
0.61
1.08
0.84-1.39
1.00
0.85-1.16
Sex
TNM stage 0.73
Differentiation grade 0.62
Site of origin 0.98
Tumor size 0.44
Age at time of diagnosis 0.25
Surgical margins 0.17
P-values are determined by a chi-square test unless otherwise indicated: * Fisher’s exact test.
85