汉黄芩素对胰腺癌作用的体外、体内实验研究
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陈双秀, Email: cshuangxiu@126.com

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湖南省科学技术厅科技计划资助项目(2009SK3152)。


In vitro and in vivo study of effect of wogonin on pancreatic cancer
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    摘要:

    目的:探讨汉黄芩素对胰腺癌Panc-1细胞体内外生长的影响。方法:将不同浓度(1,10,100 μmol/L)汉黄芩素作用胰腺癌Panc-1细胞24 h,用MTT法和流式细胞仪检测细胞的增殖与凋亡情况。将20只荷Panc-1细胞移植瘤裸鼠随机均分为对照组,汉黄芩素组(汉黄芩素60 mg/kg,1次/d),吉西他滨组(吉西他滨150 mg/kg,1次/周)与联合用药组(汉黄芩素+吉西他滨),连续给药2周并停药7 d后,比较各组移植瘤生长情况,用免疫组化法检测瘤组织微血管密度(MVD)与血管内皮生长因子(VEGF)的表达。结果:与无处理的对照细胞比较,3个浓度汉黄芩素处理后的Panc-1细胞OD值均明显降低,凋亡率均明显升高,且均呈浓度依赖性(均P<0.05)。与对照组比较,汉黄芩素组,吉西他滨组与联合用药组移植瘤的生长均被明显抑制,抑瘤率分别为24.8%,30.5%,66.1%,联合用药组的抑制率明显大于两个单药组(均P<0.05),但两单药组间差异无统计学意义(P>0.05);3个治疗组肿瘤组织CD31(反映MVD)与VEGF的表达均明显减少,且吉西他滨组,汉黄芩素组,联合用药组减少程度依次明显,组间差异均有统计学意义(均P<0.05)。结论:汉黄芩素能抑制胰腺癌细胞的增殖并促进凋亡;能一定程度抑制胰腺癌在体内的生长,并增加肿瘤对化疗药物的敏感性,该作用的机制部分与抑制肿瘤的血管生成有关。

    Abstract:

    Objective: To investigate the influence of wogonin on the growth of pancreatic cancer Panc-1 cells in vitro and in vivo. Methods: Panc-1 cells were exposed to different concentrations (1, 10 and 100 μmol/L) of wogonin for 24 h, and the cell proliferation and apoptosis were determined by MTT assay and flow cytometry. Twenty nude mice bearing Panc-1 cell xenografts were equally randomized into control group, wogonin treatment group (wogonin 60 mg/kg, daily), gemcitabine treatment group (gemcitabine 150 mg/kg, weekly) and combination treatment group (wogonin plus gemcitabine). After 2 consecutive weeks of treatment and 7 d discontinuation, the growth statuses of the tumor xenografts among groups were compared, and the microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in the tumor tissues were detected by immunohistochemical staining. Results: Compared with untreated control cells, the OD values were decreased and apoptotic rates were increased significantly in Panc-1 cells treated with any of the 3 concentrations of wogonin, and both effects presented a concentration-dependent manner (all P<0.05). Compared with control group of mice, the tumor graft growth in mice of wogonin treatment group, gemcitabine treatment group and combination treatment group were all remarkably suppressed, and the tumor suppression rate was 24.8%, 30.5% and 66.1% respectively, which was significantly higher in combination treatment group than that in either of the single-drug treatment groups (both P<0.05), but showed no statistical difference between the two single-drug treatment groups (P>0.05); the intratumoral CD31 (reflecting MVD) and VEGF expressions in all three treatment groups were significantly reduced with the degrees tending to be more evident in order of gemcitabine treatment group, wogonin group and combination treatment group, and the difference between any two groups had a statistical significance (all P<0.05). Conclusion: Wogonin can inhibit proliferation and induce apoptosis in pancreatic cancer cells in vitro; in a certain degree, it can suppress the growth of pancreatic cancer in vivo and enhance the sensitivity of pancreatic cancer to chemotherapy drugs which may be associated with its action of reducing tumor angiogenesis.

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陈双秀|刘刚|李先霞.汉黄芩素对胰腺癌作用的体外、体内实验研究[J].中国普通外科杂志,2013,22(9):1152-1157.
DOI:10.7659/j. issn.1005-6947.2013.09.010

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  • 收稿日期:2013-05-12
  • 最后修改日期:2013-08-19
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  • 在线发布日期: 2013-09-15