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新城疫病毒抑制糖酵解途径并诱导乳腺癌细胞死亡。

Newcastle disease virus suppress glycolysis pathway and induce breast cancer cells death.

作者信息

Al-Ziaydi Ahmed Ghdhban, Al-Shammari Ahmed Majeed, Hamzah Mohammed I, Kadhim Haider Sabah, Jabir Majid Sakhi

机构信息

Department of Medical Chemistry, College of Medicine, University of Al-Qadisiyah, Al Diwaniyah, Iraq.

Department of Experimental Therapy, Iraqi Center of Cancer and Medical Genetics Research, Mustansiriyah University, Baghdad, Iraq.

出版信息

Virusdisease. 2020 Sep;31(3):341-348. doi: 10.1007/s13337-020-00612-z. Epub 2020 Jun 27.

Abstract

Newcastle disease virus (NDV) can modulate cancer cell signaling pathway and induce apoptosis in cancer cells. Cancer cells increase their glycolysis rates to meet the energy demands for their survival and generate ATP as the primary energy source for cell growth and proliferation. Interfering the glycolysis pathway may be a valuable antitumor strategy. This study aimed to assess the effect of NDV on the glycolysis pathway in infected breast cancer cells. Oncolytic NDV attenuated AMHA1 strain was used in this study. AMJ13 and MCF7 breast cancer cell lines and a normal embryonic REF cell line were infected with NDV with different multiplicity of infections (moi) to determine the IC50 of NDV through MTT assay. Crystal violet staining was done to study the morphological changes. NDV apoptosis induction was assessed using AO/PI assay. NDV interference with the glycolysis pathway was examined through measuring hexokinase (HK) activity, pyruvate, and ATP concentrations, and pH levels in NDV infected and non-infected breast cancer cells and in normal embryonic cells. The results showed that NDV replicates efficiently in cancer cells and spare normal cells and induce morphological changes and apoptosis in breast cancer cells but not in normal cells. NDV infected cancer cells showed decreased in the HK activity, pyruvate and ATP concentrations, and acidity, which reflect a significant decrease in the glycolysis activity of the NDV infected tumor cells. No effects on the normal cells were observed. In conclusion, oncolytic NDV ability to reduce glycolysis pathway activity in cancer cells can be an exciting module to improve antitumor therapeutics.

摘要

新城疫病毒(NDV)可调节癌细胞信号通路并诱导癌细胞凋亡。癌细胞会提高其糖酵解速率以满足生存所需的能量需求,并产生ATP作为细胞生长和增殖的主要能量来源。干扰糖酵解途径可能是一种有价值的抗肿瘤策略。本研究旨在评估NDV对感染的乳腺癌细胞中糖酵解途径的影响。本研究使用了溶瘤性NDV减毒AMHA1株。用不同感染复数(moi)的NDV感染AMJ13和MCF7乳腺癌细胞系以及正常胚胎REF细胞系,通过MTT法测定NDV的半数抑制浓度(IC50)。进行结晶紫染色以研究形态学变化。使用AO/PI法评估NDV诱导的凋亡。通过测量NDV感染和未感染的乳腺癌细胞以及正常胚胎细胞中的己糖激酶(HK)活性、丙酮酸、ATP浓度和pH水平,检测NDV对糖酵解途径的干扰。结果表明,NDV在癌细胞中高效复制,对正常细胞无影响,并诱导乳腺癌细胞发生形态学变化和凋亡,但对正常细胞无此作用。感染NDV的癌细胞中HK活性、丙酮酸和ATP浓度以及酸度降低,这反映出感染NDV的肿瘤细胞糖酵解活性显著降低。未观察到对正常细胞有影响。总之,溶瘤性NDV降低癌细胞中糖酵解途径活性的能力可能是改善抗肿瘤治疗的一个令人兴奋的模块。

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