全 文 ：［Foundat ion］ This project was supported by National Natural Science Foundation of China（81160401, 30660212, 2008CC009）
［Br ief in t roduct ion］ Chen Peng（1974- ), male, native in Kunming Yunnan, PhD, Associate Prefessor, major research field is
cardiovascular pharmacology.
［Cor responding aut hor］ Shen Zhi- qiang．E- mail: shzhq21cn@yahoo.com.cn
Effect s of Geraniin on Pla t e le t Aggregat ion and In t er act ions
between Pla t e le t s and Neut rophils
CHEN Peng1），LI Fan1），HE Bo1），WUHong－xiang1），YANG Jian－yu2）， ZHANGXiao－chao1），
SHEN Zhi－qiang 1）
（1） School of Pharmaceutical Science，Kunming Medical University，Kunming Yunnan 650500；2） Dept. of
Pharmacology，Haiyuan Faculty of Kunming Medical University，Kunming Yunnan 650106，China）
［Abstract］ Objective To investigate the effects of geraniin on platelet aggregation and platelet- neutrophil
interactions．Methods Platelet aggregation， in vitro and ex vivo，was determined by use of Born’s method，
and the binding of thrombin- stimulated platelets to neutrophils was observed based on the rosette assay．Intracellular
calcium concentration of platelets was measured by using Fura- 2- AM. Results Geraniin in vitro significantly
inhibited arachidonic acid（AA） -， adenosine diphosphate（ADP） -， or platelet activating factor（PAF）
- induced platelet aggregation， in a concentration- dependent manner．The medium inhibitory concentrations
（IC50） were 2.4， 0.4 and 1.1 μmol/L，respectively. Intragastric geraniin at 5 mg/kg markedly suppressed platelet
aggregation induced by AA，ADP，or PAF．Geraniin decreased the total rise of [Ca2+]i，Ca2+ release，and Ca2+
influx，in a concentration- dependant manner．The IC50 values were 71.9，84.9，and 62.9 μmol/L，respectively.
Geraniin decreased the binding of thrombin- stimulated platelets to neutrophils，and significantly inhibited washed
platelet aggregation stimulated by fMLP- activated neutrophils. The IC50 values were 3.2 and 10.2 μmol/L，
respectively．Conclus ion It is suggested that geraniin inhibited platelet aggregation in vitro and ex vivo，
decreased the calciummobilization of platelets，and suppressed the interactions between platelets and neutrophils.
［Key words］ Geraniin；Platelet aggregation；Calcium；Platelet- neutrophil interactions
Previously， platelets were considered to be the
main cells involved in the pathogenesis of thrombosis，
whereas only a minor role was attributed to neutrophils.
However， many recent investigations realized that
neutrophils not only participate in thrombus formation
but may also exert a direct action on the extension of
myocardial infarction by releasing several cytotoxic
factors[1]. The interactions of platelet and neutrophil may
be one of the key factors in the development of
thromboembolic diseases [2]. It is more valuable，
therefore， to develop an antithrombotic drug especially
at an angle of influencingmultiple cellular interactions.
Geraniin was extracted and isolated from Phyllanthus
urinaria， a Chinese medicinal herbal plant rich in
Yunnan Province．In our previous study，geraniin was
found to show anti- osteoporotic effect due to its
inhibition of osteoclastic bone resorption [3]．
Interestingly， geraniin showed potent inhibition of
platelet aggregation in the in vitro screening of
antiplatelet agents．In the present study，the effects of
geraniin were investigated on arachidonic acid（AA）
-， adenosine diphosphate（ADP） -， or platelet
activating factor（PAF） - induced platelet aggregation
in vitro and ex vivo， platelet calcium mobilization，
platelet- neutrophil adhesion， and washed platelet
aggregation induced by N- formyl- methiongl－leucyl－
phenylalanine（fMLP） - activated neutrophils.
1 Mat er ia ls and Met hods
1.1 Animals
Healthy rabbits weighing 2.0- 3.0 kg，were offered
Journal of Kunming Medical University
CN 53 -1049/ R
昆明医科大学学报 2012，（5）：4 ～ 10
by the Experimental Animal Center of Kunming Medical
University（ SCXK2009008）．The protocol of this
study was approved by the Ethics Committee of Kun-
mingMedical University.
1.2 Drugs and chemicals
Geraniin was extracted from Phyllanthus urinaria，
a Chinese medicinal herbal plant rich in Yunnan
Province of China （purity: 99%） （Fig.1）．It was
dissolved in dimethyl sulphoxide（DMSO）， pH 7.0.
Crystalline aspirin was purchased from Sigma Chemical
Co. It was dissolved in 100 mmol/L Na2CO3 before use.
ADP，AA，PAF，human thrombin， Fura- 2- AM，
and fMLP were all from Sigma Chemical Co.ADP，
AA，and PAF were dissolved in phosphate buffer solu-
tion（PBS）， 100 mmol/L Na2CO3， and Tris- NaCl
buffer solution containing 0.25% bovine serum albu-
min，respectively. fMLP was dissolved in DMSO.
Fig. 1 St ruct ure of Geraniin
1.3 Preparat ion of plat e le t s
Blood sample from rabbit carotid artery was col-
lected into plastic tubes， anticoagulated with 2.7%
edetic acid（for the binding of platelets to neutrophils）
or 3.8% sodium citrate acid（for platelet aggregation）.
Platelet- rich plasma（PRP） and platelet- poor plasma
（PPP） were obtained by the centrifuging the blood at
180×g and 1 000×g，respectively，for 10 min．PRP
was further spun to pellet platelets at 1 000×g for 10
min．Platelet pellets were washed three times and re-
suspended in PBS（containing 1.0 % bovine serum al-
bumin and 1 mmol/L CaCl2）．Cell viability by Typan
blue exclusion was above 95% and cell counter was ad-
justed to 108 cell/mL.
1.4 Preparat ion of neut rophils
Neutrophils were isolated from the remaining blood
by dextran sedimentation and followed by Ficoll- Hy-
paque（specific density 1.077 g/mL） and hypotonic
lysis of erythrocytes．The cell pellet was resuspended
in an erythrocyte lysis buffer composed of 155 mmol/L
NH4Cl，2.96 mmol/L KHCO3，and 3.72 mmol/L edetic
acid．The tube was gently inverted and after 5 min the
suspension was centrifuged at 350 × g for 10 min，
and the cell pellet was washed in PBS lacking calcium;
then resuspended in Hanks’solution containing 1
mmol/L CaCl2. Cells were adjusted to a count of 2 ×
106cell/mL. Cells prepared in this manner contained 98
% neutrophils and were 96% viable.
1.5 Plat e le t aggregat ion
1.5.1 Plat elet aggregat ion in vit ro Platelet aggre-
gation in PRP was measured as described by Born [4].
The maximal aggregation was monitored （final concen-
tration of ADP 3 μmol/L，AA 0.35 mmol/L，and PAF
7.2 nmol/L） in a Lumiaggregometer．Percentage inhi-
bition by drugs was calculated by use of the following e-
quation:
Inhibition of aggregation （%） = A - BA ×100
Where A is the maximum change of tubidity when
the control （saline） is added and B is the maximum
change of tubidity when the drug（geraniin or aspirin）
is added.
1.5.2 Plat e le t aggregat ion ex vivo Rabbits
were randomly divided into 3 groups of six. Group A
was given intragastrically the same volume of saline.
Group B was administered intragastrically 5 mg/kg
geraniin，and group C 5 mg/kg aspirin．PRP and PPP
were prepared before administration and at 60，120，
180，and 240 min after administration， respectively.
Platelet aggregation induced by ADP，AA or PAF was
monitored as in vitro test， respectively.
1.6 Measurement of cyt osolic Ca 2+
The above prepared washed platelets were then
loaded with 3 μmol/L Fura- 2- AM by incubating the
suspension at 37 ℃ for 45 min. The external calcium
was adjusted by addition of 1 mmol/L CaCl2 or egtazic
acid， respectively. Intracellular Ca2+ concentration of
platelets was measured by using Fura- 2- AM[5] with a
spectrofluorophotometer（Model RF- 5000，Shimazh-
CHEN Peng，et al．Effects of Geraniin on Platelet Aggregation and Interactions between Platelets and Neutrophils 5第 5期
第 33卷6
*P < 0.05，**P < 0.01，compared with 0.5 % DMSO.
Platelet Aggregation（%）
0.5% 78.2± 6.7 73.7±7.5 65.3±7.1 69.2±3.4 69.6±2.3 67.2±3.7
DMSO
0.16 74.7±6.1 65.3±5.2 42.7±2.5* 66.3±5.5 52.7±5.8* 67.3±2.4
0.8 49.2±5.4* 51.5±3.3* 22.3±4.4** 67.2±4.1 31.5±1.8** 60.7±4.2
4 31.8±3.6** 37.4±2.9** 13.7±1.6** 60.6±6.1 20.9±5.7** 62.9±1.8
20 10.4±2.2** 28.5±4.2** 4.6±1.1** 67.9±5.7 9.6±2.7** 59.8±6.6
100 1.7±0.2** 15.6±3.6** 0.8±0.2** 62.9±4.9 1.8±1.1** 64.9±4.1
Drug（μmol/L） AA ADP PAF
Geraniin Aspirin Geraniin Aspirin Geraniin Aspirin
u，Japan） at 37℃ and magnetically stirred.
AA（200 μmol/L） - stimulated rise in [Ca2+]i was
measured separately in the presence of 1 mmol L CaCl2
or egtazic acid. The rise in [Ca2+]i in the presence of
CaCl2 1 mmol/L represents a combination of Ca2+
release and influx of Ca2+. The rise in the presence of
egtazic acid 1 mmol/L reflects Ca2+ release．The
difference between these two measurement reflects the
influx of external Ca2+.
1.7 Roset t e assay
The method of Hamburger[6]was modified. Briefly，
50 μL aliquots of platelet suspension were placed in
microtiter wells and exposed to 10 μL of 1.2 U/mL
human thrombin（final concentration: 0.2 U/mL） for
15 min at room temperature without stirring. The
platelets were then fixed with 50 μL of 2%
paraformaldehyde for 30 min at room temperature.
When required，50 μL of 0.9% saline or drug solution
was added before thrombin activation．Platelets were
washed three times with PBS and resuspended in 50 μL
PBS．Then 100 μL of neutrophils was added to the
platelet suspension and incubated for 30 min at 4 ℃
under rocking condition. One hundred neutrophils were
scored for the presence （two or more platelets per
neutrophil） or absence （zero or one platelet per
neutrophil） of platelets. Neutrophils bearing two or
more platelets were thus defined as rosettes．For each
assay， done in triplicate， the rosetting score was
assessed by two different observers.
1.8 Plat e le t aggregat ion induced by t he sup-
ernat an t from act ivat ed neut rophils
Activated neutrophil supernatant was obtained by
adding fMLP（2 μmol/L） into neutrophil suspension
for 10 min at 37℃，and then centrifuged at 3 000× g
for 1 min．Washed platelets were incubated with 0.9%
saline or drug solution for 10 min at 37℃，then added
5 μL of the cell- free supernatant of activated
neutrophils. Platelet aggregation was determined as
above described.
1.9 St at ist ical analysis
The data were analyzed by the software bag of SPSS
（Version 13，SPSS Inc.，USA）.All the data were exp-
ressed as x±s，and analyzed by one way ANOVA and
least- significant difference（LSD） test， respecti -
vely．Differences were considered statistically
significant when P < 0.05.
2 Result s
2.1 Effect s of geran iin on plat e le t aggregat -
ion in vit ro
Geraniin significantly inhibited AA- induced
platelet aggregation in a concentration- dependent man-
ner．The IC50 value was 2.4 μmol/L．On ADP- or PA-
F- induced platelet aggregation， geraniin also had
significant influence，obtaining 0.4 and 1.1 μmol/L of
IC50 values， respectively. Aspirin concentration －
dependently suppressed platelet aggregation induced by
AA （IC50 = 6.3 μmol/L），but not by ADP or PAF
（Table 1）.
Tab. 1 Effect s of geraniin on AA-，ADP-，or PAF- induced rabbit plat elet aggregat ion in vit ro ［n＝6，（x±s）］
昆明医科大学学报
Drug Concentration（μmol/L） Total rise of [Ca2+]i（nmol/L） Ca2+ release（nmol/L） Ca2+ influx（nmol/L）
0.5% DMSO 0 282.3±46.8 143.8±29.4 169.4±31.2
0.16 293.5±51.2 156.7±30.4 172.6±40.2
0.8 273.6±32.5 131.8±31.5 155.4±24.1
4 219.6±38.5* 120.6±19.5* 135.2±27.6*
20 208.9±28.6* 115.8±27.5** 120.3±21.7*
100 182.9±22.2** 112.8±20.7** 129.6±24.6*
Varapamil 100 153.8±23.4** 99.6±19.4** 95.3±18.5**
Drug Dose(mg/kg)
Platelet Aggregation（%）
0 min 60 min 120 min 180 min 240 min
AA
Saline - 75.6±5.9 72.9± 6.7 78.2± 3.7 74.2± 5.1 73.8±6.4
Aspirin 5 73.6±6.1 33.5±3.8** 19.8±4.7** 42.5±6.2** 70.4±6.6
Geraniin 5 77.1±5.5 30.7±4.2** 10.5±2.8** 29.5±4.4** 72.8±1.4
ADP
Saline - 62.3±3.9 66.4±5.7 60.8±4.9 65.0±4.6 59.8±3.3
Aspirin 5 60.8±4.1 62.8±1.5 63.7±4.8 60.4±5.5 63.7±2.9
Geraniin 5 65.0±3.7 50.4±4.6* 30.7±2.4** 36.9±2.7** 55.9±6.7
PAF
Saline - 61.3±5.1 64.8±2.4 62.4±1.9 60.8±6.9 61.7±2.5
Aspirin 5 60.5±2.2 63.9±7.1 69.6±6.5 62.2±41 62.9±5.5
Geraniin 5 64.8±5.5 46.9±4.3* 38.7±2.1** 59.6±3.3 63.7±3.8
Tab. 2 Effect of in t r agast r ic 5 mg/kg geraniin on AA-， ADP-，or PAF- induced rabbit plat elet aggregat ion
［n＝6，（x±s）］
*P < 0.05，**P < 0.01，compared with saline or 0 min.
Tab. 3 Effect of geraniin on cyt osolic calcium induced by arachidonic acid ( 200 μmol/L) in washed rabbit
plat elet s ［n＝6，（x±s）］
CHEN Peng，et al．Effects of Geraniin on Platelet Aggregation and Interactions between Platelets and Neutrophils 7第 5期
2.2 Effect of in t r agast r ic geran iin on plat e l-
e t aggregat ion ex vivo
5 mg/kg of geraniin and aspirin showed marked in-
hibitory effect on AA- induced platelet aggregation dur-
ing 60～180 min after administration. Geraniin also had
markedly inhibitory effects on platelet aggregation in-
duced by ADP as well as PAF，during 60- 180 min and
60 - 120 min after administration， respectively. As-
pirin， however， had no significant effect either by
ADP or by PAF（Table 2）.
2.3 Effect of geran iin on plat e le t cyt osolic
calcium
Geraniin decreased the total rise of [Ca2+]i，Ca2+
release，and Ca2+ influx，in a concentration- dependant
manner．The IC50 values were 71.9，84.9， and 62.9
μmol/L， respectively. Varapamil significantly lowered
[Ca2+]i elevation （Table 3）.
*P < 0.05, **P < 0.01, compared with 0.5 % DMSO.
2.4 Effect of geran iin on t he binding betwe-
en plat e le t s and neut rophils
Geraniin and aspirin significantly decreased the
binding of platelets to neutrophils with IC50 of 3.2 and
25.5 μmol/L，respectively（Table 4）.
2.5 Effect of geran iin on washed plat e le t ag-
gregat ion induced by act ivat ed neu-
t rophils
Geraniin markedly inhibited washed platelet ag-
gregation induced by the supernatant from fMLP- acti-
Drug （mol/L）
Adhesion （%）
Geraniin Aspirin
0.5% DMSO 70.5±12.3 72.9±10.5
0.16 65.8±8.2 60.3±9.7
0.8 41.3±5.1** 52.3±4.9*
4 22.8±4.3** 45.6±2.4**
20 15.9±1.8** 36.5±4.5**
100 10.2±3.4** 30.8±2.6**
Tab. 4 Effect of geraniin on t he binding of t hrom-
bin- act ivat ed plat elet s t o neut rophils ［n＝6，
（x±s）］
*P＜0.05，**P < 0.01，compared with 0.5 % DMSO
Drug（μmol/L）
Platelet Aggregation（%）
Geraniin Aspirin
0.5 % DMSO 55.2±3.6 54.3±3.7
0.16 56.2±2.7 53.3±3.1
0.8 42.6±3.9* 51.6±2.2
4 20.4±3.7* 59.6±3.7
20 12.7±2.9* 52.7±1.8
100 8.6±1.4* 56.9±4.6
Tab. 5 Effect of geraniin on washed plat elet aggrega-
t ion st imulat ed by t he supernat ant of
fMLP- act ivat ed neut rophils in r abbit s ［n＝6，
（x±s）］
*P＜0.05，compared with 0.5 % DMSO
vated neutrophils. The IC50 value was 10.2 μmol/L.
Aspirin had no inhibitory activity on platelet aggregation
stimulated by fMLP - activated neutrophils（Table 5） .
3 Discussion
ADP，AA，and PAF can cause platelet activation
and result in platelet aggregation through different path-
ways [7- 9]. In this study， geraniin in vitro significantly
inhibited AA-，ADP-，or PAF- induced platelet ag-
gregation，in a concentration- dependent manner．In-
tragastric geraniin had a significant inhibitory effect on
AA- induced aggregation 60- 120 min after administra-
tion．Differing from aspirin，geraniin also significantly
inhibited ADP- or PAF- induced platelet aggregation
60- 180 min and 60- 120 min after administration，re-
spectively．Platelet hyperfunction is believed to be as-
sociated with thrombotic disorders. It is suggested that
geraniin showed a nonspecific inhibition on platelet ag-
gregation and might be useful for antithrombosis.
After activation of platelets by thrombin， platelet
selectin is rapidly redistributed to the cell surface during
granulation， and mediates the binding of activated
platelets to neutrophils [10]. Aspirin was reported not to
inhibit expression of platelet selectin [11]. However， it
strongly inhibited ADP- stimulated platelet release of
both granule and dense granule contents．Our data in-
dicated that aspirin inhibited platelet- neutrophil adhe-
sion．Aspirin may suppress secondary expression of
other adhesion molecule on platelet surface and reduce
platelet- neutrophil adhesion．Geraniin significantly
decreased the binding of platelets to neutrophils obtain-
ing a lower IC50 value to that of aspirin. Platelet- neu-
trophil adhesion is obviously increased in some cardio-
vascular diseases [2]. The adhesion between these two
kinds of blood cells are involved in the process of throm-
bomodulation [12]. Activation of platelets increases neu-
trophil adhesion to foreign surfaces，neutrophile aggre-
gation，lysosomal enzyme release，etc. Platelet- derived
products are able to promote neutrophil chemotaxsis，
enzyme release，and phagocytosis and to inhibit oxida-
tive burst．On the other hand， neutrophil- derived
products can promote platelet aggregation， serotonin
release and generation of thrombotic materials [13]．
Thrombus formation is mediated by the platelet- neu-
trophil interactions including cell binding and platelet
aggregation[2]. Clinical studies showed that platelet- neu-
trophil rosette in patients with thrombotic disease signif-
icantly increased [11]. Our results suggest that geraniin
showed the ability to suppress the binding of activated
platelets to neutrophils， and may be beneficial to the
treatment of thromboembolic disorders.
Bioactive substances derived from activated neu-
trophils can challenge platelet aggregation， thrombox-
ane A2 formation， and cytoplasmic Ca2+ movement [14].
Aspirin，however， had no influence on platelet aggre-
gation stimulated by activated neutrophils， suggesting
that cyclooxygenase may not be directly involved in neu-
trophil- induced platelet aggregation． Toxic oxygen
radicals， cathepsin G， elastase and PAF have been
suggested to act as mediators of neutrophil- dependent
platelet activation [10]. Geraniin exerted a concentra-
tion- dependent inhibitory effect on platelet aggregation
induced by the cell- free supernatant from fMLP －
activated neutrophils．Briefly， geraniin suppressed
昆明医科大学学报 第 33卷8
CHEN Peng，et al．Effects of Geraniin on Platelet Aggregation and Interactions between Platelets and Neutrophils 9第 5期
platelet- neutrophil interaction through different
mechanism from aspirin.
Calcium is an important mediator in platelet
activation as well as in the process of platelet －
neutrophil interactions [14]．In this study， the increase
of [Ca2+]i induced by AA in the presence of CaCl2 was
much larger than that in the absence of extracellular
Ca2+， suggesting that the major component of the
AA- induced increase in [Ca2+]i is caused by the influx of
Ca2+ ions across the plasma membrane．Geraniin
concentration- dependently lowered the increase of
[Ca2+]i stimulated by AA in the presence of CaCl2 or
EGTA， respectively．This demonstrated that geraniin
inhibited both the influx of extracellular calcium and the
mobilization of calcium from intracellular stores.
Decreasing cytosolic calcium is one of the mechanisms
of geraniin in suppressing platelet hyperfunction and the
interactions between platelets and neutrophils.
In conclusion， geraniin inhibited platelet
aggregation in vitro and ex vivo， decreased platelet－
neutrophil adhesion， and suppressed platelet
aggregation induced by activated neutrophils. Geraniin
may be developed as an antithrombotic agent due to its
antiplatelet effect and suppression of platelet- neutrophil
interactions.
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（2012－02－10收稿）
［基金项目］国家自然科学基金资助项目（81160401, 30660212, 2008CC009）
［作者简介］陈鹏（1974～），男，云南昆明市人，博士，副教授，主要从事心血管药理学的研究工作．
［通讯作者］沈志强．E- mail:shzhq21cn@yahoo.com.cn.
老鹳草素对血小板聚集和血小板 - 中性粒细胞之间相互作用的影响
陈 鹏 1），李 璠 1），何 波 1），武鸿翔 1），杨建宇 2），张小超 1），沈志强 1）
（1） 昆明医科大学药学院，云南昆明 650500；2） 昆明医科大学海源学院，云南昆明 650106）
［摘要］ 目的 研究老鹳草素抗血小板聚集作用及其对血小板与中性粒细胞之间相互作用的影响．方法 采
用 Born方法观测老鹳草素在体内和体外对家兔血小板聚集功能的影响，运用玫瑰花结实验测定血小板与中性粒细
胞的黏附反应，以 Fura- 2- AM为荧光指示剂，检测老鹳草素对激活的血小板内钙水平的影响．结果 老鹳草素在
体外呈浓度依赖性明显抑制花生四烯酸（AA）、腺苷二磷酸（ADP） 及血小板活化因子（PAF） 诱导的血小板聚
集功能．其半数抑制浓度（IC50） 分别为 2.4、0.4和 1.1 μmol/L；5 mg/kg的老鹳草素灌胃亦明显抑制 AA、ADP和
PAF诱导的血小板聚集；老鹳草素显著降低洗涤血小板内钙离子浓度、减少细胞外钙内流及内钙释放，其 IC50分
别为 71.9、84.9、62.9 μmol/L．老鹳草素明显阻抑凝血酶激活的血小板与中性粒细胞之间的黏附作用，并抑制肉
豆蔻佛波醇（fMLP） 激活的中性粒细胞上清液诱导的血小板聚集功能，其 IC50分别为 3.2和 10.2 μmol/L．结论
老鹳草素明显抑制血小板聚集功能，降低血小板内钙水平，同时阻抑血小板与中性粒细胞之间的相互作用．
［关键词］老鹳草素；血小板聚集；细胞内钙；血小板 - 中性粒细胞相互作用
［中图分类号］ R973［文献标识码］ A［文章编号］ 1003－4706
除术的化疗，其目的是通过化疗减少微转移而提
高生存率．
4.3 肺癌的分子靶向治疗
肺癌的分子靶向治疗（molecular targeted thera-
py） 是指针对肿瘤发生发展过程中的细胞信号传导
和其它生物学途径的治疗手段．其作用靶点可以
是细胞表面的生长因子受体或细胞内信号传导通
路中的蛋白质．广义的分子靶点则包括参与肿瘤
细胞分化周期、凋亡、迁移、浸润，淋巴转移，
全身转移等过程中从 DNA到蛋白或酶水平的任何
亚细胞分子．主要包括表皮生长因子受体 （epi-
dermal growth factor receptor，EGFR） 家族抑制剂、
血管生成抑制剂、多靶点的酪氨酸激酶抑制剂等
几类药物．
EGFR和其配体通常在非小细胞肺癌（no small
cell lung cancer，NSCLC） 中过度表达，但在小细
胞肺癌（small cell Lung cancer，SCLC） 中几乎不
表达．成为分子靶向治疗的重要目标．目前靶向
作用于 EGFR 的因子主要包括酪氨酸激酶抑制剂
（TKI），如吉非替尼（Gefitin ib；Iressa） 和埃罗替
尼（Erlotinib；Tarceva），单克隆抗体如西妥昔单
抗（Erb ituk；C etuxim ab） 等．
血管内皮生长因子（VEGF） 家族包含 6个生
长因子 （VEGFA、B、C、D、E 以及胎盘生长因
子） 和 3 个 受 体 [VEGFR1（Flt1）、 VEGFR2
（KDR/Flk1） 和 VEGFR3（Flt4） ]．VEGF 的过度
表达与肿瘤进展及不良预后相关．目前针对 VEGF
途径的治疗包括抗 VEGF 单克隆抗体和 VEG-
FR- TKI 两大类．代表药物包括贝伐单抗 （Beva-
cizumab; Avastin）、西妥昔单抗 （Cetuximab） 和血
管内皮抑制素（Endostar）．
肺癌分子靶向治疗的出现，为肺癌患者带来新
的希望，而且为肺癌的治疗提供了一种全新的思
路．靶向治疗药物与当前手术、放疗、化疗和其
他靶向治疗药物联合治疗的疗效及安全性需进一
步评估．笔者应该坚信，随着分子生物学及分子
病理学等基础研究、临床试验技术和其他相关技
术的不断发展，肺癌分子靶向治疗药物的开发和
临床应用会达到更加成熟的阶段，对肺癌的治疗
可能产生深远的意义．以手术为主的综合治疗 /个
体化治疗是肺癌治疗的主要手段．
（2012－02－10收稿）
第 33卷10
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（上接第 3页）
昆明医科大学学报