Res@ZIF-90 suppress gastric cancer progression by disturbing mitochondrial homeostasis

IF 5 2区 医学 Q2 Medicine Translational Oncology Pub Date : 2024-11-06 DOI:10.1016/j.tranon.2024.102179
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Abstract

Background

Gastric cancer (GC) is still a serious threat to human health worldwide. As a natural compound, resveratrol has been proven to have anti-tumor activity, and the nano-delivery carrier has shown its excellent ability to retain and control drug release.

Methods

Res@ZIF-90 underwent synthesis via a one-pot method and subsequent characterization encompassing Dynamic Light Scattering, Scanning Electron Microscope, Transmission Electron Microscope, and UV–vis absorption spectroscope. The release of resveratrol from Res@ZIF-90 across varied pH environments were delineated employing High Performance Liquid Chromatography. The mitochondrial targeting of Res@ZIF-90 was scrutinized utilizing Fluorescent Inverted Microscopy. The cytotoxic impact of Res@ZIF-90 on HGC-27 cells was evaluated through CCK-8 assay, Live/Dead staining, scratch test, and JC-1 assay. Furthermore, the HGC-27 tumor-bearing mice model was established to explore the anti-tumor effect of Res@ZIF-90.

Results

ZIF-90 can effectively release resveratrol under acidic (pH = 5.5) conditions. In addition, Res@ZIF-90 could be taken up by cells and localized into mitochondria. ZIF-90 has no obvious cytotoxicity at the experimental concentration, while Res@ZIF-90 was more cytotoxic to HGC-27 cells than free resveratrol at the same concentration. Res@ZIF-90 significantly reduced the expressions of PGCS 1α, TFAM, PINK1, and COX IV, which together induced mitochondrial homeostasis disorders and inhibited the tumor growth of HGC-27 tumor-bearing mice in vivo.

Conclusions

Res@ZIF-90 can inhibit the progression of gastric cancer by targeting the mitochondria of gastric cancer cells and disrupting mitochondrial homeostasis to produce cytotoxic effects. Res@ZIF-90 may be a promising antitumor drug with potential application value.
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Res@ZIF-90 通过扰乱线粒体平衡抑制胃癌进展
背景胃癌(GC)仍然严重威胁着全球人类的健康。Res@ZIF-90通过一锅法合成,随后进行了动态光散射、扫描电子显微镜、透射电子显微镜和紫外-可见吸收光谱等表征。利用高效液相色谱分析了 Res@ZIF-90 在不同 pH 值环境下白藜芦醇的释放情况。利用荧光倒置显微镜观察了 Res@ZIF-90 的线粒体靶向性。Res@ZIF-90对HGC-27细胞的细胞毒性影响通过CCK-8试验、活/死染色、划痕试验和JC-1试验进行了评估。此外,还建立了 HGC-27 肿瘤小鼠模型,以探讨 Res@ZIF-90.ResultsZIF-90 在酸性(pH = 5.5)条件下能有效释放白藜芦醇的抗肿瘤作用。此外,Res@ZIF-90还能被细胞吸收并定位到线粒体中。在实验浓度下,ZIF-90 没有明显的细胞毒性,而在相同浓度下,Res@ZIF-90 对 HGC-27 细胞的细胞毒性高于游离白藜芦醇。Res@ZIF-90可通过靶向胃癌细胞线粒体,破坏线粒体平衡产生细胞毒性作用,从而抑制胃癌的进展。Res@ZIF-90可能是一种具有潜在应用价值的抗肿瘤药物。
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来源期刊
CiteScore
8.40
自引率
2.00%
发文量
314
审稿时长
54 days
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
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