Overexpression of cannabinoid receptor 2 is associated with human breast cancer proliferation, apoptosis, chemosensitivity and prognosis via the PI3K/Akt/mTOR signaling pathway

大麻素受体 2 的过度表达通过 PI3K/Akt/mTOR 信号通路与人类乳腺癌增殖、凋亡、化学敏感性和预后相关

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作者:Qiang Song, Wenjin Zhang, Dan Shi, Zhiliang Zhang, Qiurong Zhao, Mengyuan Wang, Man Huang, Juanjuan Meng, Wei Cui, Xiaohe Luo

Conclusions

These findings reveal that CB2 mediates BC via the PI3K/Akt/mTOR signaling pathway. CB2 could be a novel target for the diagnosis and treatment of BC.

Methods

We examined the expression and prognostic significance of CB2 in BC tissues by qPCR, second-generation sequencing, western blot, and immunohistochemistry. We assessed the impacts of overexpression and a specific agonist of CB2 on the growth, proliferation, apoptosis, and drug resistance of BC cells in vitro and in vivo using CCK-8, flow cytometry, TUNEL staining, immunofluorescence, tumor xenografts, western blot, and colony formation assays.

Results

CB2 expression was significantly lower in BC compared with paracancerous tissues. It was also highly expressed in benign tumors and ductal carcinoma in situ, and its expression was correlated with prognosis in BC patients. CB2 overexpression and treatment of BC cells with a CB2 agonist inhibited proliferation and promoted apoptosis, and these actions were achieved by suppressing the PI3K/Akt/mTOR signaling pathway. Moreover, CB2 expression was increased in MDA-MB-231 cell treated with cisplatin, doxorubicin, and docetaxel, and sensitivity to these anti-tumor drugs was increased in BC cells overexpressing CB2. Conclusions: These findings reveal that CB2 mediates BC via the PI3K/Akt/mTOR signaling pathway. CB2 could be a novel target for the diagnosis and treatment of BC.

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