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p53 调控多糖对耐药性卵巢癌细胞的细胞毒性

The p53 Modulated Cytotoxicity of Polysaccharide Against Resistance Ovarian Cancer Cells.

作者信息

Amini Elaheh, Baharara Javad, Afzali Mahbube, Nikdel Najme

机构信息

Department of Cellular & Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.

Department of Biology, Research Center for Animal Development Applied Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.

出版信息

Avicenna J Med Biotechnol. 2019 Jul-Sep;11(3):208-214.

PMID:31379992
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6626503/
Abstract

BACKGROUND

Marine environment is a valuable source of bioactive compounds with variable medicinal properties. Previously, it was shown that extracted polysaccharide has prominent cytotoxic effect on HeLa human cervical cancer cells. In the present study, the anti-cancer properties of polysaccharide extracted from ( were examined in comparison with paclitaxel as a conventional drug against resistant ovarian cancer; also, its related mechanism against A2780cp ovarian cancer cells was investigated.

METHODS

The A2780cp cancer cells and NIH3T3 normal cells were cultured and treated with different concentrations of polysaccharide extracted from for 24 and 48 . Then, cell toxicity was studied by MTT assay, morphology of cells was observed under inverted microscopy and the type of induced cancer cell death was assessed by annexin V-FITC, propodium iodide and acridine orange staining. Finally, the apoptosis pathway was determined by measurement of caspase-3 and caspase-9 activity and assessment of p53 and Bcl-2. The statistical analysis was performed by SPSS software, one way ANOVA and p<0.05 was considered significant.

RESULTS

Our observations from MTT assay and morphological assessment exhibited that isolated polysaccharide inhibited proliferation of ovarian cancer cells with IC of 35 , while paclitaxel suppressed tumor cell growth with IC=10 . In contrast, MTT observations revealed low cytotoxicity of these chemotherapeutic agents against NIH3T3 normal cells. Also, the analysis correlated with induced cell death elucidated that concurrent treatment of polysaccharide plus paclitaxel had a further anti-cancer effect against A2780cp cells mainly through restoration of p53 and mitochondrial apoptosis cell death induction.

CONCLUSION

Taken together, our research supports the finding that application of polysaccharide extracted from can be considered a promising marine chemotherapeutic approach for advancing efficacy of paclitaxel in treatment of resistant ovarian cancer. Additional experiments are required to elucidate the role of brittle star polysaccharides in animal and clinical trials.

摘要

背景

海洋环境是具有多种药用特性的生物活性化合物的宝贵来源。此前研究表明,提取的多糖对人宫颈癌HeLa细胞具有显著的细胞毒性作用。在本研究中,对从[具体名称未给出]提取的多糖的抗癌特性与作为抗耐药卵巢癌的传统药物紫杉醇进行了比较研究;此外,还研究了其针对A2780cp卵巢癌细胞的相关作用机制。

方法

培养A2780cp癌细胞和NIH3T3正常细胞,并用不同浓度的从[具体名称未给出]提取的多糖处理24小时和48小时。然后,通过MTT法研究细胞毒性,在倒置显微镜下观察细胞形态,并通过膜联蛋白V - FITC、碘化丙啶和吖啶橙染色评估诱导癌细胞死亡的类型。最后,通过测量半胱天冬酶 - 3和半胱天冬酶 - 9活性以及评估p53和Bcl - 2来确定凋亡途径。采用SPSS软件进行统计分析,单因素方差分析,p<0.05被认为具有统计学意义。

结果

我们从MTT法和形态学评估中观察到,分离出的多糖抑制卵巢癌细胞增殖,IC50为35μg/mL,而紫杉醇抑制肿瘤细胞生长的IC50 = 10μg/mL。相比之下,MTT观察结果显示这些化疗药物对NIH3T3正常细胞的细胞毒性较低。此外,与诱导细胞死亡相关的分析表明,多糖加紫杉醇联合处理对A2780cp细胞具有进一步的抗癌作用,主要是通过恢复p53和诱导线粒体凋亡细胞死亡。

结论

综上所述,我们的研究支持以下发现:应用从[具体名称未给出]提取的多糖可被视为一种有前景的海洋化疗方法,以提高紫杉醇治疗耐药卵巢癌的疗效。需要进一步的实验来阐明脆海星多糖在动物和临床试验中的作用。

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