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大麻素和标准化大麻提取物通过 FAK/MAPK/Akt/NF-κB 信号通路抑制 MCF-7 细胞迁移、侵袭并诱导细胞凋亡。

Cannabinoids and standardized cannabis extracts inhibit migration, invasion, and induce apoptosis in MCF-7 cells through FAK/MAPK/Akt/NF-κB signaling.

机构信息

Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai 90112, Thailand.

Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla, Hat-Yai 90112, Thailand.

出版信息

Toxicol In Vitro. 2023 Dec;93:105667. doi: 10.1016/j.tiv.2023.105667. Epub 2023 Aug 23.

DOI:10.1016/j.tiv.2023.105667
PMID:37625625
Abstract

BACKGROUND

Breast cancer is the highest incidence of all types of cancer in women, and the cancer metastasis process accounts for a majority of cancer deaths. Two major cannabinoids, Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), from Cannabis sativa are expected to have anti-cancer activity. This study aimed to investigate the effects of THC, CBD, and standardized cannabis extracts (F1, F2, and F3) on migration, invasion, and apoptosis of human breast cancer (MCF-7) cells.

METHODS

Cell viability, survival, and apoptosis were determined using the MTT, clonogenic, and nuclear staining assays, respectively, while cancer cell migration and invasion were evaluated by the wound healing, trans-well, and filopodia assays. Western blot analysis was used to find out the mechanisms of the cannabinoids against MCF-7 cells.

RESULTS

CBD, THC, and F1 inhibited filopodia formation, migration, and invasion of MCF-7 cells through suppressing the expression of the FAK, Akt, ERK1/2, p38MAPKs, and NF-κB upstream pathways, as well as inhibiting the Rac1/Cdc42 downstream pathways. In addition, CBD significantly inhibited the mTOR pathway. Furthermore, CBD and F1 induced apoptosis in MCF-7 cells via the Bcl-2/caspase-3 pathways.

CONCLUSION

These results indicate that THC, CBD, and F1 have great abilities for preventing breast cancer cell metastasis in in vitro experiments.

摘要

背景

乳腺癌是女性所有癌症中发病率最高的,而癌症转移过程导致了大多数癌症患者的死亡。大麻中的两种主要大麻素,Δ-9-四氢大麻酚(THC)和大麻二酚(CBD)有望具有抗癌活性。本研究旨在探讨 THC、CBD 和标准化大麻提取物(F1、F2 和 F3)对人乳腺癌(MCF-7)细胞迁移、侵袭和凋亡的影响。

方法

通过 MTT、集落形成和核染色测定分别测定细胞活力、存活和凋亡,而通过划痕愈合、Transwell 和丝状伪足测定评估癌细胞迁移和侵袭。使用 Western blot 分析来寻找大麻素对 MCF-7 细胞的作用机制。

结果

CBD、THC 和 F1 通过抑制 FAK、Akt、ERK1/2、p38MAPKs 和 NF-κB 上游途径的表达,以及抑制 Rac1/Cdc42 下游途径,抑制 MCF-7 细胞的丝状伪足形成、迁移和侵袭。此外,CBD 显著抑制了 mTOR 途径。此外,CBD 和 F1 通过 Bcl-2/caspase-3 途径诱导 MCF-7 细胞凋亡。

结论

这些结果表明,THC、CBD 和 F1 在体外实验中具有很强的预防乳腺癌细胞转移的能力。

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