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梁若笳,应家乐,朱磊.羟基红花黄色素A对卵巢癌细胞PI3K/Akt信号通路的影响[J].浙江中西医结合杂志,2019,29(5):
羟基红花黄色素A对卵巢癌细胞PI3K/Akt信号通路的影响
Effect of hydroxysafflower yellow A on PI3K/Akt signaling pathway in ovarian cancer
投稿时间:2019-01-19  修订日期:2019-02-12
DOI:
中文关键词:  羟基红花黄色素A(HSYA)  卵巢癌  顺铂耐药  PI3K/Akt  化疗敏感性
英文关键词:Hydroxy safflower yellow A (HSYA)  qvarian cancer  cisplatin resistance  PI3K/Akt  Chemotherapy sensitivity
基金项目:浙江省自然科学基金(LY15H270011)
作者单位E-mail
梁若笳* 浙江省中医院
浙江中医药大学 
7452818@qq.com 
应家乐 浙江中医药大学  
朱磊 浙江中医药大学  
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中文摘要:
      [目的] 研究羟基红花黄色素A(hydroxysafflor yellow A,HSYA)对人顺铂耐药的卵巢癌A2780/DDP细胞株顺铂耐药性的逆转作用及具体机制。[方法]培养A2780/DDP细胞,接种至20只裸鼠,随机分为对照组、红花组、顺铂组和联合组共4个组,均采用腹腔注射的给药方式,对照组予0.9%氯化钠溶液,顺铂组按3mg·kg-1剂量给予顺铂,红花组按1.1g·kg-1给予HSYA,联合组予HSYA(1.1g·kg-1)联合顺铂(3mg·kg-1),每3天给药1次,连续给药4周。第5周后处死小鼠,解剖取瘤记录瘤重并计算抑瘤率,HE染色观察各组肿瘤的病理改变,Western blot检测Akt、p-Akt蛋白表达。[结果]对照组瘤重4.71±0.17g,顺铂组瘤重3.53±0.28g,抑瘤率25.08%,红花组瘤重4.54±0.25g,抑瘤率3.61%联合组瘤重2.76±0.17g,抑瘤率41.36%。与对照组和顺铂组相比,联合组的肿瘤重量显著下降(P<0.05),抑瘤率明显增加(P<0.05);HE染色显示联合组与顺铂组比较肿瘤坏死程度更高;Western blot结果示,对照组Akt蛋白相对表达水平为0.61±0.11,顺铂组为0.62±0.09,红花组为0.42±0.10,联合组为0.44±0.07。与对照组比较,顺铂组Akt、p-Akt蛋白表达无统计学差异(P>0.05),与对照组与顺铂组比较,红花组与联合组的Akt、p-Akt蛋白表达较低,差异有统计学意义(P<0.05)。[结论]HSYA能通过下调PI3K/AKT通路的关键组分Akt、p-Akt蛋白,来增强A2780/DDP对顺铂的化疗敏感性,逆转顺铂耐药。
英文摘要:
      [Objective] To investigate the reversal effect of hydroxysafflor yellow A (HSYA) on cisplatin resistance in human ovarian cancer cells A2780/DDP and its specific mechanism.[ Methods] A2780/DDP cells were cultured and inoculated to 20 mice. Divided all mice into control group, cisplatin group, HSYA group and combined group randomly. Control group was given 0.9% NaCl, cisplatin group was given cisplatin at a dose of 3 mg/kg, HSYA group was given HSYA at a dose of 1.1g·kg-1, and combined group was given HSYA (1.1g·kg-1) combined with cisplatin (3 mg·kg-1). Intraperitoneal injection was used for 4 weeks continuously, once every 3 days. Five weeks later, killed mice for removing the tumors. The tumor weight was recorded and the tumor inhibition rate was calculated. The HE staining was used to observe the pathological changes of the tumors, and Western blot was used to detect the protein contents of Akt and p-Akt. [Results] The tumor weight of the control group was 4.71 ±0.17g, that of the cisplatin group was 3.53 ±0.28g, the inhibition rate was 25.08%, that of the safflower group was 4.54 ±0.25g, the inhibition rate was 3.61%, and that of the combined group was 2.76 ±0.17g, the inhibition rate was 41.36%.Compared with control group and cisplatin group, the weight of tumor in combined group was reduced (P<0.05) while the tumor inhibition rate was significantly increased (P<0.05). HE staining showed that the degree of tumor necrosis was higher in combined group than in the cisplatin group. Western blot results showed that the relative expression level of Akt protein in control group was 0.61±0.11, cisplatin group was 0.62 ±0.09, safflower group was 0.42 ±0.10, and combination group was 0.44 ±0.07. Compared with the control group, the expression of Akt and p-Akt protein in cisplatin group had no significant difference (P > 0.05). Compared with the control group and cisplatin group, the expression levels of Akt and p-Akt protein in safflower group and combination group were lower, and the difference was statistically significant (P < 0.05). [Conclusion] HSYA can not only enhances the chemosensitivity of A2780/DDP to cisplatin but also reverses Cisplatin-Resistant by down-regulating Akt and p-Akt proteins which are the key components of PI3K/AKT pathway.
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