摘要
目的探讨川芎嗪联合顺铂对Lewis肺腺癌组织生长及血管生成的抑制作用。方法建立Lewis肺癌小鼠移植瘤模型,随机分为对照组、川芎嗪组、顺铂组、联合组,每组14只。对照组予以腹腔注射0.9%Na Cl 0.2 m L,qd;顺铂组予以腹腔注射2 mg·kg^(-1)顺铂0.2 m L,qd;川芎嗪组予以腹腔注射100mg·kg^(-1)川芎嗪0.2 m L,qd;联合组予以腹腔注射100 mg·kg^(-1)川芎嗪+2 mg·kg^(-1)顺铂,共0.2 m L,qd。4组均连续给药14 d。用透射电镜观察肿瘤组织超微结构并计算肿瘤坏死率,用Western blot检测1型血小板结合蛋白基序的解聚素样金属蛋白酶(ADAMTS1)和血管内皮生长因子(VEGF)蛋白的表达,观察并记录微血管密度蛋白(CD105)染色结果。结果川芎嗪组、顺铂组、联合组和对照组的肿瘤坏死率分别为(15.58±3.19)%,(24.64±11.96)%,(31.76±15.20)%,(9.37±1.36)%;ADAMTS1表达水平分别为(0.57±0.02),(0.79±0.01),(0.98±0.02),(0.48±0.01);VEGF蛋白表达水平分别为(0.64±0.01),(0.42±0.01),(0.28±0.01),(0.87±0.03);CD105蛋白表达水平分别为(2.90×10~4±5.50×10~3),(2.50×10~4±4.90×10~3),(1.40×10~4±6.20×10~3),(4.90×10~4±7.30×10~3),川芎嗪组、顺铂组和联合组的上述指标与对照组比较差异均有统计学意义(P<0.05)。结论川芎嗪和顺铂均能明显抑制肺腺癌移植瘤的生长,两者联用具有协同作用,其可能通过降低VEGF的表达,升高ADAMTS1的表达和抑制微血管生成,来发挥抗肿瘤血管生成的作用。
Objective To investigate the inhibitory effect of tetrameth- ylpyrazine（TMP） , a Chinese medicine, in combination with cisplatin （DDP） on the tumor growth and angiogenesis in mouse Lewis lung cancer. Methods Lewis lung carcinoma model of C57BL/6 were produced by intraperitoneal injection of Lewis lung cancer cells in right axillary 0. 2 mL. Then the 56 tumor -bearing mice were randomized into 4 groups. Control group was given with 0. 9% NaCl 0. 2 mL by peritoneal injection, qd. DDP group was given with 2 mg . kg-1 DDP 0. 2 mL by peritoneal injection, qd. TMP group was given with 100 mg .kg-1 TMP 0. 2 mL by peritoneal injection, qd. Combination group was given with 100 mg . kg -1 TMP ＋ 2 mg . kg-1 DDP by peritoneal injection, per 0. 2 mL, qd. Before dosing every time, the dosage was adjusted according toweight, lasting 14 successive days. Different treatments were served from day 5 transplantation and all mice were sacririced after 19 days. Subcutaneous tumors were processed for tumor weight ,the tumor necrosis rate of each group were calculated,and observed the ultrastructure of tumor tissue under electron microscopy and photographed the record, the expressions of a disintegrin and metalloproteinase with thrombospondin type I motif （ ADAMTS1 ）, vascular endothelial growth factor（VEGF） were detected by Western blot, and recorded the results of CD105. Results The main indexes in TMP, DDP, combination and control groups were compared. The tumor necrosis rates were （15.58 ± 3.19）%, （24.64 ± 11.96）%, （31.76 ± 15.20）%, （9.37± 1.36）%; the expression levels of ADAMTS1 were （0.57±0.02）, （0.79 ± 0.01）, （0.98 ± 0.02）, （0.48 ± 0.01）; the expression levels of VEGF were （0.64 ± 0. 01 ）, （0.42 ± 0.01 ）, （0.28 ±0. 01 ）, （0. 87 ± 0.03 ） ; the expression levels of CD105 were （2.90 × 10^4 ±5.50×10^3）, （2.50×10^4±4.90×10^3）, （1.40×10^4±6.20×10^3）, （4.90×10^4±7.30×10^3）, with statistically significant difference （ P 〈 0. 05 �
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2016年第22期2085-2088,共4页
The Chinese Journal of Clinical Pharmacology
关键词
川芎嗪
肺腺癌
1型血小板结合蛋白基序的解聚素样金属蛋白酶
血管内皮生长因子
微血管密度
tetramethylpyrazine
lung carcinoma
a disintegrin and metalloproteinase with thrombospondin type Ⅰmotif
vascular endothelial growth factor
microvascular density
