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双生子姜黄素抑制 4T1 癌细胞增殖,并调节 Balb/c 小鼠模型中凋亡和转移基因的表达。

Gemini curcumin inhibits 4T1 cancer cell proliferation and modulates the expression of apoptotic and metastatic genes in Balb/c mice model.

机构信息

Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran; Interfaculty Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, 72076 Tübingen, Germany.

出版信息

Pathol Res Pract. 2023 Mar;243:154344. doi: 10.1016/j.prp.2023.154344. Epub 2023 Jan 24.

Abstract

BACKGROUND

Despite the attractive anti-cancer effects, poor solubility and low bioavailability have restricted the clinical application of Curcumin. Recent findings show that Gemini nano-curcumin (Gemini-Cur) significantly improves the cellular uptake of Curcumin and its anti-cancer effect in tumor cells. Here, we aimed to assess the suppressive effect of Gemini-Cur on 4T1 breast cancer cells in vitro and, subsequently, in BALB/c mouse models.

MATERIALS AND METHODS

Fluorescence microscopy was employed to visualize cellular uptake and morphological changes of 4T1 cells during treatment with Gemini-Cur and void curcumin. MTT and annexin V/FITC assays were performed to study the toxic effect of Gemini-Cur on mouse cancer cells. For in vivo studies, BALB/c tumor-bearing mice were used to evaluate the inhibitory effect of Gemini-Cur in comparison with mice receiving free Curcumin and nanoparticles.

RESULTS

Our data showed that Gemini-Cur enters the cells and inhibits proliferation in a time- and dose-dependent manner. Annexin V/FITC confirmed apoptotic effect on 4T1 cells. In vivo studies also illustrated that tumor growth is suppressed in Gemini-Cur treated mice rather than controls. Expression studies demonstrated the modulation of apoptotic and metastatic genes, including Bax, Bcl-2, MMP-9, VEGF, and COX-2 in treated mice.

CONCLUSION

In conclusion, these data demonstrate the promising anti-cancer properties of Gemini-Cur on mice models. However, further studies at molecular and cellular levels are required to conclude this therapeutic advantage.

摘要

背景

尽管姜黄素具有诱人的抗癌作用,但由于其溶解度低和生物利用度低,限制了其在临床上的应用。最近的研究结果表明,双子星纳米姜黄素(Gemini-Cur)显著提高了姜黄素的细胞摄取率及其在肿瘤细胞中的抗癌作用。在这里,我们旨在评估 Gemini-Cur 对体外 4T1 乳腺癌细胞的抑制作用,并随后在 BALB/c 小鼠模型中进行评估。

材料与方法

荧光显微镜用于观察 Gemini-Cur 和空姜黄素处理 4T1 细胞时的细胞摄取和形态变化。MTT 和 Annexin V/FITC 检测用于研究 Gemini-Cur 对小鼠癌细胞的毒性作用。体内研究中,使用 BALB/c 荷瘤小鼠来评估 Gemini-Cur 与接受游离姜黄素和纳米粒子的小鼠相比的抑制效果。

结果

我们的数据表明,Gemini-Cur 进入细胞并以时间和剂量依赖的方式抑制增殖。Annexin V/FITC 证实了对 4T1 细胞的凋亡作用。体内研究还表明,在 Gemini-Cur 治疗的小鼠中,肿瘤生长受到抑制,而不是对照小鼠。表达研究表明,凋亡和转移基因(包括 Bax、Bcl-2、MMP-9、VEGF 和 COX-2)在治疗小鼠中受到调节。

结论

总之,这些数据表明 Gemini-Cur 在小鼠模型中具有有前途的抗癌特性。然而,需要进一步在分子和细胞水平上进行研究,以得出这种治疗优势的结论。

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