Induction of apoptosis and role of paclitaxel-loaded hyaluronic acid-crosslinked nanoparticles in the regulation of AKT and RhoA.
Induction of apoptosis and role of paclitaxel-loaded hyaluronic acid-crosslinked nanoparticles in the regulation of AKT and RhoA.
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DOI：
10.4103/japtr.japtr_26_20
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发表时间：
2020-07
影响因子：
1.4
通讯作者：
Muhammad TST
中科院分区：
文献类型：
--
作者：
Chaudhry GE;Akim A;Zafar MN;Abdullah MA;Sung YY;Muhammad TST
癌症是一种复杂的多因素疾病，也是世界范围内的主要死亡原因。尽管开发了许多抗癌药物，但由于严重的副作用，生存率仍会降低。常规药物的非靶向方法是毒性背景下的主要参与者之一。Hybryonan是一种多功能的生物聚合物和癌细胞上受体（CD 44）的配体。透明质酸-紫杉醇（HA-PTX）处理的MCF-7和HT-29癌细胞株显示出明显的凋亡形态学特征。流式细胞术分析表明，HA-PTX诱导细胞凋亡作为一种重要的细胞死亡模式。PTX处理后MCF-7中肿瘤抑制蛋白（p53）的活化水平增加，但HT-29中未观察到变化，可能是由于遗传突变。AKT和Rho A蛋白缺乏抑制表明在未来的研究中使用可能的抑制剂，这可能在增加药物对突变细胞系的敏感性和降低癌细胞存活、迁移和转移的可能性方面发挥作用。
Cancer is a complex multifactorial disease and leading causes of death worldwide. Despite the development of many anticancer drugs, there is a reduced survival rate due to severe side effects. The nontargeted approach of convention drugs is one of the leading players in context to toxicity. Hyaluronan is a versatile bio-polymer and ligand of the receptor (CD44) on cancer cells. The MCF-7 and HT-29 cancer cell lines treated with hyaluronic acid-paclitaxel (HA-PTX) showed the distinguishing morphological features of apoptosis. Flow cytometric analysis showed that HA-PTX induces apoptosis as a significant mode of cell death. The activation level of tumor suppressor protein (p53) increased after PTX treatment in MCF-7, but no changes observed in HT-29 might be due to hereditary mutations. The lack of suppression in AKT and Rho A protein suggest the use of possible inhibitors in future studies which might could play a role in increasing the sensitivity of drug towards mutated cells line and reducing the possibilities for cancer cell survival, migration, and metastasis.