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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 ligustrazine and cisplatin on the growth and angiogenesis in Lewis lung adenocarcinoma. Methods The mouse model of Lewis lung cancer was established and randomly divided into control group, ligustrazine group, cisplatin group and combination group, with 14 mice in each group. The rats in the control group were injected intraperitoneally with 0.9% NaCl 0.2 m L qd, while the cisplatin group was intraperitoneally injected with 2 mg · kg -1 cisplatin 0.2 m L qd. The rats in the Ligustrazine group were intraperitoneally injected with 100 mg · kg ~ (-1) 1) Ligustrazine 0.2 m L, qd; the combination group was given intraperitoneal injection of 100 mg · kg -1 ligustrazine + 2 mg · kg -1 cisplatin for a total of 0.2 m L qd. All the four groups were administrated continuously for 14 days. The ultrastructure of tumor tissue was observed by transmission electron microscopy and tumor necrosis rate was calculated. Western blot was used to detect the expression of type 1 platelet-associated protein motifs (ADAMTS1) and vascular endothelial growth factor (VEGF) Record microvessel density protein (CD105) staining results. Results Tumor necrosis rates of ligustrazine group, cisplatin group, combination group and control group were (15.58 ± 3.19)%, (24.64 ± 11.96)%, (31.76 ± 15.20)%, (9.37 ± 1.36)%, respectively. ADAMTS1 expression The levels of VEGF protein were (0.67 ± 0.02), (0.79 ± 0.01), (0.98 ± 0.02) and (0.48 ± 0.01) , (0.87 ± 0.03), respectively. The expression levels of CD105 protein 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). There was significant difference between the above indexes in the ligustrazine group, the cisplatin group and the combined group as compared with the control group (P <0.05). Conclusion Both tetramethylpyrazine and cisplatin can significantly inhibit the growth of human lung adenocarcinoma xenografts, and the synergistic effect of them can reduce the expression of VEGF, increase the expression of ADAMTS1 and inhibit the angiogenesis of lung adenocarcinoma Role.