Synergistic Induction of Apoptosis in HeLa CellSynergistic Induction of Apoptosis in HeLa Cell
s by the Proteasome Inhibitor Bortezomib and s by the Proteasome Inhibitor Bortezomib and
Histone Deacetylase Inhibitor SAHAHistone Deacetylase Inhibitor SAHA
Yizhou Jiang, Yi Wang, Zijie Su, Ling Yang, Weiwei Guo, Ji Zuo Yizhou Jiang, Yi Wang, Zijie Su, Ling Yang, Weiwei Guo, Ji Zuo
INTRODUCTIONINTRODUCTION
• Bortezomib: Proteasome inhibitor
• Suberoylanilide hydroxamic, SAHA: His
tone deacetylase inhibitor
• HeLa cells
0
50
100
0: 5 1: 4 2: 3 1: 1 3: 2 4: 1 5: 0
Effect Ratio
Cell
Via
bilit
y (%
)
BTZ+SAHA
a b
c
Combination of Bortezomib and SAHA Inhibits HeLa Cell GrowthCombination of Bortezomib and SAHA Inhibits HeLa Cell Growth
0
20
40
60
80
100
2.5 5 10 20 40 80
[BTZ] nM
Cel
l Via
bilit
y (%
)
BTZ
0
20
40
60
80
100
1 2 4 6 8 10
[SAHA] mM
Cell
Via
bilit
y (%
)
SAHA
0
25
50
75
100
Control BTZ SAHA B+S
Apo
ptot
ic C
ells
(%)
Giemsa
Hoechst
a c
b d* *
Combination of Bortezomib and SAHA Induces HeLa Cell ApoptosisCombination of Bortezomib and SAHA Induces HeLa Cell Apoptosis
* ** *
A B
DC
A
B
C
A
B
C
a c
b d
0
1
2
3
4
5
Control BTZ SAHA B+S
bax/
bcl-
2 mR
NA r
atio
0.0
0.2
0.4
0.6
0.8
1.0
1.2
Control BTZ SAHA B+S
rela
tive
gen
e ex
pres
sion
leve
l of
bcl
-2
0.0
1.0
2.0
3.0
4.0
5.0
Control BTZ SAHA B+S
rela
tive
gen
e ex
pres
sion
lev
el o
f ba
x
*
0.0
0.5
1.0
1.5
2.0
2.5
Control BTZ SAHA B+S
rela
tive
exp
ress
ion
leve
l of
bax
pro
tein
0.0
0.2
0.4
0.6
0.8
1.0
1.2
Control BTZ SAHA B+Srela
tive
exp
ress
ion
leve
l of
bcl-
2 pr
otei
n
0
1
2
3
4
5
Control BTZ SAHA B+S
bax/
bcl-
2 pr
otei
n ra
tio* *
*
Combination of Bortezomib and SAHA Enhances Bax/bcl-2 RatioCombination of Bortezomib and SAHA Enhances Bax/bcl-2 Ratio
a
b
Combination of Bortezomib and SAHA Inhibits NFCombination of Bortezomib and SAHA Inhibits NFB Nuclear TrB Nuclear Translocation and Downregulates Akt/p-Aktanslocation and Downregulates Akt/p-Akt
Akt and NF-Akt and NF-B Signaling PathwaysB Signaling Pathways
CONCLUSIONCONCLUSION
Bortezomib + SAHA
Synergistic Induction of Apoptosis In HeLa
Promising Rationale for Treating Cervical Cancer
Akt, p-Akt, NF-B↓; bax/bcl-2↑; caspase-3↑
THANK YOU
