9-Hexadecenoic acid inhibits the aggressiveness of gastric cancer via targeting PTPN1/FTH1 signaling.

IF 1.8 4区医学 Q3 ONCOLOGY

Anti-Cancer Drugs Pub Date : 2025-04-18 DOI:10.1097/CAD.0000000000001724

Xin Wang, Haiyan Peng

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引用次数: 0

Abstract

9-Hexadecenoic acid (9-HA) possesses anti-tumor properties. However, the effects of 9-HA on gastric cancer are scarcely reported. The present study aimed to investigate the effects of 9-HA on gastric cancer. mRNA levels were detected by reverse transcription quantitative PCR. Protein expression was detected by western blot. Cell behaviors were analyzed using Cell Counting Kit-8, colony formation, transwell, and propidium iodide staining assays. Co-localization of PTPN1 and FTH1 was determined using fluorescence in situ hybridization assay. In vivo assay was conducted to further verify the effects of 9-HA on gastric cancer. 9-HA suppressed the malignant behavior of gastric cancer. Moreover, 9-HA promoted iron-overload-dependent ferroptosis of gastric cancer in vivo and in vitro. Traditional Chinese medicine systems pharmacology predicted that 9-HA could target PTPN1, which was upregulated in gastric cancer cells. PTPN1-mediated phosphorylation of FTH1 contributed to the latter degradation. Overexpressed PTPN1 alleviated the effects of 9-HA, promoting the aggressiveness of gastric cancer and suppressing tumor cell ferroptosis. Interestingly, overexpressed PTPN1 antagonized the effects of 9-HA, promoted tumor growth, and inhibited the ferroptosis of gastric cancer. In summary, 9-HA-mediated downregulation of PTPN1 drives ferroptosis and inhibit the aggressiveness of gastric cancer. Thence, 9-HA may be an alternative strategy for gastric cancer.

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9-十六烯酸通过靶向PTPN1/FTH1信号抑制胃癌的侵袭性。

9-十六烯酸（9-HA）具有抗肿瘤特性。然而，9-HA对胃癌的作用鲜有报道。本研究旨在探讨9-HA对胃癌的影响。采用反转录定量PCR检测mRNA水平。western blot检测蛋白表达。使用细胞计数试剂盒-8、菌落形成、transwell和碘化丙啶染色法分析细胞行为。采用荧光原位杂交法测定PTPN1和FTH1的共定位。通过体内实验进一步验证9-HA对胃癌的作用。9-HA抑制胃癌的恶性行为。此外，9-HA在体内和体外均可促进铁超载依赖性胃癌铁下垂。中医系统药理学预测9-HA可靶向胃癌细胞中上调的PTPN1。ptpn1介导的FTH1磷酸化有助于后者的降解。PTPN1过表达可减轻9-HA的作用，促进胃癌的侵袭性，抑制肿瘤细胞铁下垂。有趣的是，过表达PTPN1可拮抗9-HA的作用，促进肿瘤生长，抑制胃癌铁下垂。综上所述，9- ha介导的PTPN1下调可驱动铁下垂并抑制胃癌的侵袭性。因此，9-HA可能是胃癌的另一种治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anti-Cancer Drugs 医学-药学

CiteScore

3.80

自引率

0.00%

发文量

244

审稿时长

3 months

期刊介绍： Anti-Cancer Drugs reports both clinical and experimental results related to anti-cancer drugs, and welcomes contributions on anti-cancer drug design, drug delivery, pharmacology, hormonal and biological modalities and chemotherapy evaluation. An internationally refereed journal devoted to the fast publication of innovative investigations on therapeutic agents against cancer, Anti-Cancer Drugs aims to stimulate and report research on both toxic and non-toxic anti-cancer agents. Consequently, the scope on the journal will cover both conventional cytotoxic chemotherapy and hormonal or biological response modalities such as interleukins and immunotherapy. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.