The anticancer activities of wogonin in murine sarcoma S180 both in vitro and in vivo

The anticancer activities of wogonin in murine sarcoma S180 both in vitro and in vivo
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DOI:
10.1248/bpb.29.1132
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发表时间:
2006-06-01
影响因子:
2
通讯作者:
Wang, Xiao-Tang
Wang, Xiao-Tang
中科院分区:
医学4区
文献类型:
--
作者:
Wang, Wei;Guo, Qing-Long;Wang, Xiao-Tang

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本实验研究了汉黄芩素对小鼠肉瘤S180的体内外抗肿瘤作用,并对其促凋亡的分子机制进行了初步探讨。MTT法检测汉黄芩素对S180细胞生长的抑制作用,并呈浓度依赖性。48小时的IC 50值为(7.37 +/- 1.53)× 10(-5)m。倒置光学显微镜和荧光显微镜观察到汉黄芩素作用后S180细胞出现典型的形态学改变和凋亡泡现象。根据移植瘤研究方案,(1))小鼠移植肿瘤细胞S180。观察汉黄芩素治疗后肿瘤重量及外周血白细胞计数的变化。荷瘤小鼠外周血白细胞计数与对照组相比无明显变化。汉黄芩素40 mg/kg组抑瘤率为53.01%。DNA片段化实验显示汉黄芩素诱导小鼠S180肉瘤细胞凋亡。RT-PCR结果显示,汉黄芩素可诱导Bax和p53 mRNA表达增加,bcl-2 mRNA表达降低。Western-blot结果显示汉黄芩素可诱导Bax蛋白表达增加,bcl-2蛋白表达降低。总之,汉黄芩素能诱导小鼠S180肉瘤细胞凋亡,从而抑制肿瘤生长。其促凋亡作用可能与提高p53的mRNA水平、提高bax的mRNA和蛋白水平、降低bcl-2的mRNA和蛋白水平有关。
The anticancer effects of wogonin on murine sarcoma S180 both in vitro and in vivo were investigated, and its pro-apoptotic molecular mechanism was further studied. Wogonin treatment resulted in significant inhibition of S180 cells in a concentration-dependent manner detected by MTT assay. The IC50 value for 48h was (7.37 +/- 1.53)x10(-5)m. Typical morphological changes and apoptosis bleb phenomenon in S180 cells exposed to wogonin were distinctly observed by the inverted light microscope and the fluorescence microscope, respectively. According to protocols of transplanted tumor research,(1)) mice were transplanted with tumor cells S180. The weight of tumor and the peripheral leucocyte count were observed after the treatment of wogonin. The significant suppression of tumor growth was observed, and the peripheral leucocyte count of S180-bearing mice remained no significant changes compared with control group. After the treatment of 40 mg/kg wogonin, the inhibitory rate of tumor weight was 53.01%. Additional DNA fragmentation assay showed that wogonin induced apoptosis on murine sarcoma S180 tissue. RT-PCR results indicated that the increasing mRNA levels of bax and p53 and the decreasing mRNA level of bcl-2 were induced by wogonin. Western-blot assay showed that the increasing protein level of bax and the decreasing protein level of bcl-2 were induced by wogonin. Collectively, wogonin could induce apoptosis in murine sarcoma S180 thereby inhibiting the tumor growth both in vitro and in vivo. The pro-apoptotic effects might be related to the improvement of mRNA level of p53, the improvement of mRNA and protein levels of bax, and the reduction of mRNA and protein levels of bcl-2.