| 武向丽.紫草素对荷肝癌裸小鼠移植瘤生长的抑制作用及机制[J].安徽医药,2019,23(5):852-855. |
| 紫草素对荷肝癌裸小鼠移植瘤生长的抑制作用及机制 |
| The effects and mechanism of Shikonin on xenografts growth in liver cancer of nude mice |
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| DOI：10.3969/j.issn.1009-6469.2019.05.002 |
| 中文关键词: 肝肿瘤 紫草素 细胞凋亡 顺铂 半胱氨酸天冬氨酸蛋白酶3 bcl-2相关X蛋白质 小鼠,裸 |
| 英文关键词: Liver neoplasms Shikonin Apoptosis Cisplatin Caspase 3 Bcl-2-associated X protein Mice,nude |
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| 中文摘要: |
| 目的 研究紫草素抑制荷肝癌裸小鼠移植瘤生长的作用及其机制。方法 通过皮下注射肝癌细胞制备荷肝癌裸小鼠模型;设模型组,紫草素低、中、高剂量组和顺铂组,每组12只,分别隔天一次给予0.9%氯化钠溶液,紫草素0.5 mg/kg、1 mg/kg、2 mg/kg和顺铂2 mg/kg,共给药6次。观察动物生存状态和移植瘤组织生长状态,称量瘤重并计算抑瘤率;HE染色法进行肿瘤组织形态检查,TUNEL法进行细胞凋亡检查,免疫组织化学法观察肿瘤组织凋亡相关蛋白表达。结果 与模型组比较,紫草素各组裸小鼠食欲和精神状态都明显好转,瘤体积小、活动度低、硬度低,移植瘤组织出现片状坏死病变、移植瘤组织细胞凋亡数量明显增多,凋亡指数显著升高［(22.93±5.40)、(39.86±8.25)、(60.74±9.61)比(2.64±1.09),P＜0.05］;瘤体质量显著减轻［(1.32±0.21) g、(1.18±0.17) g、(0.83±0.12) g比(1.69±0.14) g,P＜0.05］、抑瘤率显著升高［(21.89±3.75)%、(30.18±4.92)%、(50.89±6.43)%比(0.00±0.00)%,P＜0.01］;肿瘤组织中凋亡相关蛋白［半胱氨酸天冬氨酸蛋白酶3(caspase?3)、bcl?2相关X蛋白质(Bax、bcl?2)］中的caspase?3表达显著上调［(0.16±0.05)、(0.21±0.04)、(0.27±0.06)比(0.05±0.02),P＜0.05］、Bax表达显著上调［(0.54±0.10)、(0.63±0.15)、(0.81±0.21)比(0.29±0.05),P＜0.01］,其中紫草素中、高剂量组bcl?2显著下调［(0.37±0.05)、(0.30±0.05)比(0.50±0.07),P＜0.05］,Bax/bcl?2比值显著升高［(1.17±0.25)、(1.70±0.39)、(2.71±0.68)比(0.59±0.20),P＜0.05］。结论 紫草素具有抑制荷肝癌裸小鼠移植瘤生长的作用,可能与其调节凋亡相关蛋白表达而促进细胞凋亡、诱导肿瘤组织坏死有关。 |
| 英文摘要: |
| Objective To investigate the effect of Shikonin on the growth of transplanted tumor in nude mice bearing liver cancer and its mechanism.Methods The nude mice models bearing liver cancer were made by subcutaneous injection of human liver cell line HepG2,and were treated with Shikonin (0.5,1,2 mg/kg) and Cisplatin (2 mg/kg),once every two days,for 6 times.The mice’general states and tumor growth conditions were observed,the histopathological changes of tumor tissue was observed by HE staining;the tumor cells apoptosis was detected by TUNEL;the expression of apoptosis-related protein were detected by immunohistochemistry (IHC).Results After treated with Shikonin,the diet and mental state of nude mice bearing liver cancer were improved,tumor size,activity and hardness decreased;thetumor tissue showed pathological changes such as necrosis,cell shrinkage,the number of apoptotic cells in tumor tissue increased significantly,and the apoptotic index increased significantly［(22.93±5.40),(39.86±8.25),(60.74±9.61) vs.(2.64±1.09),P＜0.05］;the tumor weight of Shikonin treated groups decreased significantly［(1.32±0.21) g,(1.18±0.17) g,(0.83±0.12) g vs.(1.69±0.14)g,P＜0.05 or P＜0.01］;the inhibition rate increased significantly［(21.89±3.75)%,(30.18±4.92)%,(50.89±6.43)% vs.(0.00±0.00)%,P＜0.01］;the expression of Bax ［(0.16±0.05),(0.21±0.04),(0.27±0.06) vs.(0.05±0.02),P＜0.05］ and caspase-3 ［(0.54±0.10),(0.63±0.15),(0.81±0.21) vs.(0.29±0.05),P＜0.01］ increased significantly,the expression of Bcl-2 protein in Shikonin (1,2mg/kg) groups decreased significantly ［(0.37±0.05),(0.30±0.05) vs.(0.50±0.07),P＜0.05］,and the ratio of Bax/Bcl-2 were increased significantly ［(1.17±0.25),(1.70±0.39),(2.71±0.68) vs.(0.59±0.20),P＜0.05］.Conclusions Shikonin inhibits the growth of xenografted liver cancer in nude mice,which may be related to the regulation of apoptosis-related protein expression,apoptosis and tumor necrosis. |
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