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安乃近、甲氧基安乃近和对乙酰氨基酚对胰腺癌细胞系PaTu 8988 t和Panc-1增殖、凋亡及坏死的影响。

Effects of metamizole, MAA, and paracetamol on proliferation, apoptosis, and necrosis in the pancreatic cancer cell lines PaTu 8988 t and Panc-1.

作者信息

Malsy Manuela, Graf Bernhard, Bundscherer Anika

机构信息

Department of Anesthesiology, University Medical Center Regensburg, Franz Josef Strauss Allee 11, 93053, Regensburg, Germany.

出版信息

BMC Pharmacol Toxicol. 2017 Dec 6;18(1):77. doi: 10.1186/s40360-017-0185-y.

Abstract

BACKGROUND

Adenocarcinoma of the pancreas is one of the most aggressive cancer diseases affecting the human body. Recent research has shown the importance of the perioperative phase in disease progression. Particularly during this vulnerable phase, substances such as metamizole and paracetamol are given as general anesthetics and postoperative analgesics. Therefore, the effects of metamizole and paracetamol on tumor progression should be investigated in more detail because the extent to which these substances influence the carcinogenesis of pancreatic carcinoma is still unclear. This study analyzed the influence of metamizole and its active metabolites MAA (4-N-methyl-aminoantipyrine) and paracetamol on the proliferation, apoptosis, and necrosis of the pancreatic cancer cell lines PaTu 8988t and Panc-1 in vitro.

METHODS

Cell proliferation was measured by means of the ELISA BrdU assay and the rate of apoptosis by flow cytometry using the Annexin V assay.

RESULTS

Metamizole and paracetamol significantly inhibited cell proliferation in pancreatic cancer cells. After the addition of metamizole to PaTu 8988t cells, the rate of apoptosis was reduced after 3 h of incubation but significantly increased after 9 h of incubation.

CONCLUSION

The oncogenic potential of pancreatic adenocarcinoma is mainly characterized by its extreme growth rate. Non-opioid analgesics such as metamizole and paracetamol are given as general anesthetics and postoperative analgesics. The combination of metamizole or paracetamol with cytotoxic therapeutic approaches may achieve synergistic effects. Further studies are necessary to identify the underlying mechanisms so that new therapeutic options may be developed for the treatment of this aggressive tumor.

摘要

背景

胰腺腺癌是侵袭人体的最具侵袭性的癌症疾病之一。最近的研究表明围手术期在疾病进展中的重要性。特别是在这个脆弱阶段,安乃近和对乙酰氨基酚等物质被用作全身麻醉剂和术后镇痛药。因此,应更详细地研究安乃近和对乙酰氨基酚对肿瘤进展的影响,因为这些物质对胰腺癌致癌作用的影响程度仍不清楚。本研究分析了安乃近及其活性代谢物MAA(4-N-甲基氨基安替比林)和对乙酰氨基酚对胰腺癌细胞系PaTu 8988t和Panc-1体外增殖、凋亡和坏死的影响。

方法

通过ELISA BrdU检测法测量细胞增殖,并使用膜联蛋白V检测法通过流式细胞术检测凋亡率。

结果

安乃近和对乙酰氨基酚显著抑制胰腺癌细胞的增殖。向PaTu 8988t细胞中加入安乃近后,孵育3小时后凋亡率降低,但孵育9小时后显著增加。

结论

胰腺腺癌的致癌潜能主要表现为其极高的生长速度。非阿片类镇痛药如安乃近和对乙酰氨基酚被用作全身麻醉剂和术后镇痛药。安乃近或对乙酰氨基酚与细胞毒性治疗方法联合使用可能会产生协同效应。有必要进行进一步研究以确定潜在机制,从而开发出治疗这种侵袭性肿瘤的新治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc0/5717838/a20c721a6ba7/40360_2017_185_Fig1_HTML.jpg

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