Cancerous inhibitor of protein phosphatase 2A(CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer(NSCLC). CIP2A plays an ’oncogenic nexus’ to partici...Cancerous inhibitor of protein phosphatase 2A(CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer(NSCLC). CIP2A plays an ’oncogenic nexus’ to participate in the tumorigenesis and chemoresistance in several cancer types. AKT and m TORC1 overactivation are detected in NSCLC and many other cancers. Previous studies found that the CIP2A/AKT/m TOR pathway controls cell growth, apoptosis, autophagy process. Polyphyllin I(PPI) and polyphyllin VII(PPVII) are natural components extracted from Paris polyphylla that display anti-cancer properties. In the present study, we investigated whether PPI and PPVII can be used in the cisplatin(DDP)-resistant human NSCLC cell line A549/DDP. Results demonstrated that PPI and PPVII treatment significantly suppressed A549/DDP cell proliferation, migration, invasion and EMT, induced apoptosis and autophagy. Further examination of the mechanism revealed that the PPI and PPVII significantly upregulated the p53, induced caspase-dependent apoptosis and suppressed the CIP2A/AKT/m TOR pathway. The activation of autophagy was mediated through PPI and PPVII induced inhibition of m TOR. We propose that PPI and PPVII might be developed as candidate drugs for DDP-resistant NSCLC.展开更多
本文初步探究了鼠李糖类似物作为靶向配体构建递药系统,实现胰腺癌主动靶向治疗的可行性。采用薄膜水化法成功制备了鼠李糖脂脂质体,并对其理化性质、体外释放特性、体内外靶向性及体外药效学进行了初步评价。鼠李糖脂脂质体在体内外均...本文初步探究了鼠李糖类似物作为靶向配体构建递药系统,实现胰腺癌主动靶向治疗的可行性。采用薄膜水化法成功制备了鼠李糖脂脂质体,并对其理化性质、体外释放特性、体内外靶向性及体外药效学进行了初步评价。鼠李糖脂脂质体在体内外均能表现出针对人胰腺癌(BxPC-3)细胞的良好靶向性,且具有更强的抗肿瘤效果。基于此,进一步以鼠李糖脂天然结构类似物重楼皂苷VII(Polyphyllin VII,PPVII)为靶向材料及活性成分,探索重楼皂苷VII脂质体(Polyphyllin VII modified liposomes,PPVII-Lip)对BxPC-3细胞的靶向性及抗肿瘤活性研究。结果表明,PPVII-Lip粒径均一,在体内对BxPC-3实体瘤有较强的靶向能力,能够提高药物在胰腺癌肿瘤部位选择性富集。在体内、外药效评价中,相比胰腺癌一线化疗药物吉西他滨,PPVII-Lip对胰腺癌细胞也表现出更强的抑制效果。综上所述,该靶向递药策略有望为靶向治疗胰腺癌的药物递送研究提供有益的思路。本研究体内动物实验得到了西南大学动物伦理委员会的批准(批准号:IACUC-20210130-2)。展开更多
基金supported by the National Natural Science Foundation of China(No.81473485)the Natural Science Foundation of Shandong Province(No.2014ZRE27321)
文摘Cancerous inhibitor of protein phosphatase 2A(CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer(NSCLC). CIP2A plays an ’oncogenic nexus’ to participate in the tumorigenesis and chemoresistance in several cancer types. AKT and m TORC1 overactivation are detected in NSCLC and many other cancers. Previous studies found that the CIP2A/AKT/m TOR pathway controls cell growth, apoptosis, autophagy process. Polyphyllin I(PPI) and polyphyllin VII(PPVII) are natural components extracted from Paris polyphylla that display anti-cancer properties. In the present study, we investigated whether PPI and PPVII can be used in the cisplatin(DDP)-resistant human NSCLC cell line A549/DDP. Results demonstrated that PPI and PPVII treatment significantly suppressed A549/DDP cell proliferation, migration, invasion and EMT, induced apoptosis and autophagy. Further examination of the mechanism revealed that the PPI and PPVII significantly upregulated the p53, induced caspase-dependent apoptosis and suppressed the CIP2A/AKT/m TOR pathway. The activation of autophagy was mediated through PPI and PPVII induced inhibition of m TOR. We propose that PPI and PPVII might be developed as candidate drugs for DDP-resistant NSCLC.
文摘本文初步探究了鼠李糖类似物作为靶向配体构建递药系统,实现胰腺癌主动靶向治疗的可行性。采用薄膜水化法成功制备了鼠李糖脂脂质体,并对其理化性质、体外释放特性、体内外靶向性及体外药效学进行了初步评价。鼠李糖脂脂质体在体内外均能表现出针对人胰腺癌(BxPC-3)细胞的良好靶向性,且具有更强的抗肿瘤效果。基于此,进一步以鼠李糖脂天然结构类似物重楼皂苷VII(Polyphyllin VII,PPVII)为靶向材料及活性成分,探索重楼皂苷VII脂质体(Polyphyllin VII modified liposomes,PPVII-Lip)对BxPC-3细胞的靶向性及抗肿瘤活性研究。结果表明,PPVII-Lip粒径均一,在体内对BxPC-3实体瘤有较强的靶向能力,能够提高药物在胰腺癌肿瘤部位选择性富集。在体内、外药效评价中,相比胰腺癌一线化疗药物吉西他滨,PPVII-Lip对胰腺癌细胞也表现出更强的抑制效果。综上所述,该靶向递药策略有望为靶向治疗胰腺癌的药物递送研究提供有益的思路。本研究体内动物实验得到了西南大学动物伦理委员会的批准(批准号:IACUC-20210130-2)。
