全 文 :2016
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Vol41,No.6 March,2016
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,Email:tanyuanguaiguai@126.com
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Advanceintreatmentofpediatricleukemiathroughmodulatingsignaling
pathwaysinducedbytraditionalChinesemedicine
TANYuan
(NeonatalDepartment,AfiliatedHospitalofGuilinMedicalUniversity,Guilin541001,China)
[Abstract] Leukemiaisthemostcommontypeofcancerinchildhood,whichisalsooneofthemalignanttumorsthatcanbe
curedbychemotherapyHowever,infectionandthesideefectsofchemotherapydrugsarethecausesofdeathinchildrenwith
leukemiaChemotherapycombinedwithtraditionalChinesemedicineisusedtotreatmentofpediatricleukemiainclinicAl
thoughtraditionalChinesemedicinehasextensiveclinicalexperienceinthetreatmentofleukemia,themechanismisnotclear
ThetargeteddrugsareatractivefortheadvantagesofthehighselectivityandlitlesideefectsTargetedtherapiesinpediatric
leukemiaaretargetingBCR/ABL,TARAandFLT3proteins,whichactivationresultsinthedownstreamactivationofmultiple
signalingpathways,includingthePI3K/AKT,JNK/STAT,Ras/ERKpathwaysInrecentyears,thetargetsiteorthesignaling
pathwaysareclearforthetraditionalChinesemedicineinthetreatmentofleukemiaInthispaper,wereviewrecentstudies,
summarythetraditionalChinesemedicineprescriptionsandefectiveingredientswhichcanregulatethesignalingpathwaysWe
viewtoprovideabasisforthetreatmentofchildhoodleukemiawithtraditionalChinesemedicinecombinedwithchemotherapy
drugsortargeteddrugs
[Keywords] leukemia;pediatricleukemia;signalingpathways;traditionalChinesemedicine
doi:10.4268/cjcmm20160603
QÇwòÉ(!ü»¢
[1]。
¡¢
(leukaemi
a)
é7¸Ã/0
,
PÃ/0¢ó
30%,
¡¢ò? ¡¢
(acuteleukaemia,AL)¨
> ¡
¢
(chronicleukaemia,CL),
¡¢«>ò
AL[2]。
F
G´¨IJ£´m
,
¡¢«=
r?pø
,
«
5
y°ý¬Ý
70%~90% [34]。
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ÐQR
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éhi°\à]
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wÒ
£\à]
(altransretinoicacid,ATRA),
më
ATRA
ôShiçÑ ò
Pin1
Ñ
[5];
r[dòhi°
BCR/ABL
T]ÒÓ±ù1UsVY
(imatinib)¨
ÝmVY
(dasat
inib)[67]。
2
d,² ¡¢÷ZGÖüh
i
,
åæ¥(ãÿÒãäp ¡¢«x»¢°
ý}
[89]。
7E
,FMS
T]ÒÓ
3(FMSliketyrosineki
nase3,FLT3)
² ¡¢$hò&çèSô
[10],FLT3
±ù1
Lestaurtinib
¡¢Bãä
[11],
F~
,
¡¢«núåænJ
[10]。
xãé
BCR/ABL
êé
FLT3,¯
Ð:Òêë>v<@N
Ras/Raf,PI3K,JAK
ö
[1214],
q
1,
1,
,¯
е¶
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[12]。
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q
1
¡¢;Öüçèv<@N
Fig1 Themaintargetpointandsignalingpathwaysinleukemia
$A,hò3%%W
,
² ¡¢$mÚÖüh
i
,
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ATO)
=_,X ¡¢«
5
yx¢°ý¬
25%
pr
95%。
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ATO
é$,XYÖü
,
XY
B_&
,¸
[þû¢
。ATO
² ¡¢$q=ú
[$`
,
åæ$=|_,Òãäp ¡¢
ý¬
[4345]。
më
ATO
Òµ¶QÄÅ(
、
¦
、
¡°ö
,
Òî×
PML/RARαÑ 、Ûê Bcl2Ü
Ý
、
_
Caspase3/8、
±ù
NFκBö,²hi@N÷
PI3K/Akt
@N¨
JNK
@NBµ¶
[16,4649],
ù{
ATO
=UsVY ¡¢«Bhi
,
¤OUsVYØ,
¡¢«B
[5051]。
r[8B_&$,D
i°»¢
,
åæ$¸hò45±ù1d@Aô
ë
、
õâËab:ö»¢
。
DËOéð
[
,
DËO² ¡¢÷Bãä
,¯
é
HSP90
±ù1
,
¡¢QÄÅ
AKT
@N¨
Notch/NF
κB@N:B±ùhi[3840],BCR/ABL[¯ ¡¢«
B
,
cÞáUsVYØ,hi
[52]。
Ü
1
¡¢$,êëv<@N
Table1 TraditionalChinesemedicinefortreatmentofleukemiaandthesignalingpathways
W¦ $, v<@N *Ë^Þ
Lt_8Z ¡¢ XY
Lt_8Z
(ATO) PI3K/AKT
@N
;JNK
@N
[16]
Qdü
、
½¡ÎFe Qd
f¬Ë
SFK/STAT5
@N
;FLT3 [1718]
*º ¡¢ *
*º
JAK/STAT3
@N
;MAPK
@N
[1923]
ËgíØ Ë
ËO
PI3K/AKT
@N
;BCR/ABL [2425]
wËOFe wË
wËO
MMP
@N
;AKT/mTOR
@N
;Raf/ERK
@N
;MAPK
@N
;;FLT3 [2629]
Ëð×&ñ Ëï
Ëï
PI3K/AKT
@N
;Notch
@N
; [3032]
vhi ¡¢ vh
vhi
GSK3β;Wnt@N [33]
m* ¡¢ m*
m*7ⅡA JAK/STAT3/5@N;AMPK/mTOR@N;Raf/ERK@N; [3435]
Ëj ¡¢ Ëj
Ëj>Å
MICA [36]
Mö¡ñ Mö
Mö>Å
JAK/STAT3 [37]
D DËO
BCR/ABL;AKT
@N
;Notch/NFκB@N [3840]
Ój
ÜÍ3jOÍ3]³
JNK
@N
;AKT
@N
;FLT3 [4142]
·099·
ò
kö
:
v<@N$, ¡¢
12
Èïd,
f¬Ëé$,Qd
,
ìQdò
Ö$,Qdüåæ¥($ ¡¢«
%
[53],
¤Of¬Ë=_,Ò*× ¡¢«
åæÜ/
[54],
fù÷f¬Ë@òêë
SFK/STAT5
@N
±ù
BCL/ABL
[¯¨_° ¡¢ÄŦ
[17],
¤O
¯é
FLT3
±ù1
[18]。
*ºé$,*Öü
,
*°Èï×&d,
,
i° ¡¢Èï×&¨l
¡¼¥
。
ì*òÖb4,* ¡¢åæ¥(
ãÿÒµ¶ ¡¢«_O&Lhi
[55]。
°*
º
Ã>
,¯
ÒÞá
ATRA
Ø,
[5657],
êë ¡¢
QÄÅ
JAK/STAT3
@N¨
AKT
@N
[20,2334]。
þhif
ùÜ{*ºUsVYö,=DBhi
。
Ëï
ò$,ËïÖü
,
²åæ¥($
,
/sBËï
、
ËïO
、
ãËï¨ãËïOËïpqi°
¡¢«
,
mëDB45mÊhi
[58]。
Ëï
¡¢QÄÅ
PI3K/AKT
@N¨
Notch
@NB±ùhi
,
Ò±ùØ,ÄÅ°°±
[3032],
²=÷
Ãu
,
6
hi@N$ì$UsVY
、ATO
ö=DB*¤
hi
。
13
¡d,
ËOé$,ËÖüð[
,
ËDB>?,
,
¡¢«_~mï
、
$¡
、
nÅöDB?$
[59],¯
éËgíØÖü
。
mëËODBe/0
、
%
、
eöhi
,
Ôä
Ü
{ ¡¢cB,
[60]。
ËOhifùÃ>
,
BCR/
ABL
[¯ ¡¢QÄÅB±ùhi
,
Òêë
BCR/ABL
2
ZÛO@N
PI3K/AKT
@N¨
MEK
@Nö
[24];
AT
RA
=iODB*¤hi
[61];
ÒÞáQÄÅUs
VYØ,
[62]。
wËOé$,wË
,¯
,
Ã>
,
?>
。
wËODB>hiçè
,
Ò
±ù
AKT/mTOR
@N¨
Raf/ERK/MAPK
@N
,
êU
sVY,hi
,
Ò±ùUsVYØ,QÄÅ°
±
;
1,
,
wËOé
FLT3
±ù1
,
QÄÅáâB
±ùhi
,
wËO>ç;X=XiO>|_,
=Xi
,
êÝrµ&hi
[2729]。
vhiò$,
vhÖü
,
còvhi ¡¢Öü
,
åæ
¥($vhi ¡¢_,=~ÒÐѨ*× ¡¢
«åæÇ®
[63]。
vhiÛê
GSK3βÜÝ,êÛ
ê
NFκBÜÝ,ê±ùQÄÅ°±[33]。m*7ⅡA
ò$,m*ð[
,
m*òb4,m* ¡
¢Öü
,
m* ¡¢³=_ ¡¢¨
¡¢Òp
,
îH&Lhi¨ÐÑ«°ý´
ö
[6465]。
m*7ⅡA BCR/ABL2ZÛOv<@N
JAK/STAT3/5
@N
、MPK/mTOR
@N
、Raf/ERK
@NöD
Bêëhi
,
Ò±ùØUsVYQÄÅ°±
[3435],
Us
VY
、TARA
¨
ATO
=DB*¤hi
[6667]。
14
Û¡d
Ëj>Åò$,Ëjð[
,
Ëjò$]Ûd$,
,
é ¡¢Û,$7¸i[
8,
[15],
éËj ¡¢Öü
,
åæ¥($
,
Ëj ¡
¢=_e/0hi
,
p ¡¢«åæ
,
ÐÑ:~
[68]。
Ëj>ÅÖüZr45êëhi
,
@
òbê
MICA
ÜÝ
NK
ÄÅìCD
[36]。
r[
Z45êëhi>ÅòMö>Å
,¯
é$,Mö
,
Möé7¸i¡d,
。
Mö>Å@òÛê
JAK/STAT3
v<@N ¡¢QÄÅZr±ùhi
[37]。
15
|d
ÜÍ3jOÍ3]³òÓj
ð[
,
òj>$7B
,
Ò±ù
FLT3
Ü
Ý
,
ìêë
JNK
@N¨
AKT
@N
[4142],
wËO=
iDB*¤hi
[69],
_,nÌO=DB
µ&
[70]。
2
<ã
FG3°()m
,
ö¥(
Ìú>Q
Ç«ý²[¯ÔÕ
,
X=·ì·>ç;,uo|b
4
。
íîuo| ¡¢ç;:3,é
BCR/
ABL
[¯«
,
ê~|ÔÕ[¯,ÊI°åæe
åæînJ
,
²1Ôäb
,
$A,Fðm
。
67° ¡
¢«$A/Z-ç÷$,£´¯_
,
ê
X=<
,
ð3%&ÔäpÛ
,
³ì
,
$,²
3÷Ôä
I°¹^nJ
。
¡¢é@ò_
ìÃ/0»¢
,
6_,&Lhi¨
$Dhéç÷ ¡¢«É(ÐÕð[
,
ê$,
q$ÒÃòBrþè
,
Õ1
,
å渵i$,³=
_,£ ¡¢
,
ÖüZrµ&
、
Þá>,
Ø,
、
f45@¨*× ¡¢«åæÇ®öh
i
。
<=íîç;,v<@N
,
N^u<úv<@
NÃò{$,
,
êò=_,p).
,
Aç
¡¢«
。
ÔV_,
5$,,hihif
ùnôõ
,
$mëú>$,~
PI3K/AKT,
JNK/STAT,Ras/ERK
öv<@NBêëhi
,
BþÒêë
>v<@N
,
ê9>=ÒÞá_,Ø,hi
,
ò
$,_=p).
,
~ ¡¢
,
b$
$,[\²ôAs:µi
,
ªú
ATO
¨D,
,
|$
,=_,eç;,7ê
。
þ{hifù
$,:ò
,
ê9¦I°Ôä
nJ
,
åæ
é
,
Ü{$,_,=µ
&hiIÿ[H
。
[
yg?z
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vww
.
Ëj>Å ¡¢ÄÅ
MICA
ÜÝ
NK
ÄÅì
CDµ¶
[D].
Åx
:
Åx
,2012.
[37]
¹Õx
,
Í¿Ñ
,
iym
,
ö
.
Mö>Å
K562
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