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S-1节拍化疗对LCI-D20肝癌血管生成的抑制作用

[Inhibition of angiogenesis of LCI-D20 hepatocellular carcinoma by metronomic chemotherapy of S-1].

作者信息

Chen Fang-guo, Wang Jie-jun, Xue Qiong

机构信息

Oncology Center, the 88th Hospital of PLA, Tai'an Shandong 271000, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2009 Sep;17(9):665-8.

PMID:19785953
Abstract

OBJECTIVE

To investigate the role of metronomic chemotherapy of S-1 on angiogenesis of hepatocellular carcinoma in animal model.

METHOD

S-1 was dissolved in a 0.5% (w/v) HPMC solution. 30 LCI-D20 were randomly devided into five groups: control group(O), 10 mg * kg(-1) * d(-1) S-1 group (A), 1 mg * kg(-1) * d(-1) S-1 group (B), 0.5 mg * kg(-1) * d(-1) S-1 group (C) and 0.25 mg * kg(-1) * d S-1 group (D). 28 days after the treatment with 0.5% (w/v) HPMC solution, tumors in LCI-D20 mice were moved out. Tumor mass was measured and microvessel density (MVD) was used to evaluate angiogenesis in tumor. The cellular apoptosis was determined using flow cytometry. The expression of VEGF, bFGF and TSP-1 was measured by RT-PCR.

RESULTS

The mean tumor mass was 2.01, 0.38, 1.12, 1.38, 2.27 g in O, A, B, C, D group, respectively. The mean MVD was 39.57, 19.90, 5.93, 17.10, 29.53 in O, A, B, C, D respectively. The mean tumor cellular apoptosis rate was 4.08%, 44.37%, 31.73%, 19.83%, and 8.25% in O, A, B, C, D respectively. The expression of VEGF and bFGF in O group was highest, and A was slightly low, and C and D taked the third place, and B was the lowst; The expression of TSP-1 in B was highest, and C and D were slightly low, and A taked the third place, and O was the lowst.

CONCLUSION

Metronomic chemotherapy of S-1 destabilizes pre-existing tumor vasculature and inhibits ongoing angiogenesis.

摘要

目的

探讨S-1节拍化疗在动物模型中对肝细胞癌血管生成的作用。

方法

将S-1溶解于0.5%(w/v)的羟丙基甲基纤维素(HPMC)溶液中。30只LCI-D20小鼠随机分为五组:对照组(O)、10mg·kg⁻¹·d⁻¹ S-1组(A)、1mg·kg⁻¹·d⁻¹ S-1组(B)、0.5mg·kg⁻¹·d⁻¹ S-1组(C)和0.25mg·kg⁻¹·d S-1组(D)。用0.5%(w/v)HPMC溶液处理28天后,取出LCI-D20小鼠体内的肿瘤。测量肿瘤质量,并使用微血管密度(MVD)评估肿瘤中的血管生成。采用流式细胞术测定细胞凋亡情况。通过逆转录聚合酶链反应(RT-PCR)检测血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)和血小板反应蛋白-1(TSP-1)的表达。

结果

O、A、B、C、D组的平均肿瘤质量分别为2.01、0.38、1.12、1.38、2.27g。O、A、B、C、D组的平均MVD分别为39.57、19.90、5.93、17.10、29.53。O、A、B、C、D组的平均肿瘤细胞凋亡率分别为4.08%、44.37%、31.73%、19.83%、8.25%。VEGF和bFGF在O组中的表达最高,A组略低,C组和D组并列第三,B组最低;TSP-1在B组中的表达最高,C组和D组略低,A组排第三,O组最低。

结论

S-1节拍化疗破坏已有的肿瘤血管系统并抑制正在进行的血管生成。

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