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Ganoderma lucidum fruiting body extracts inhibit colorectal cancer by inducing apoptosis, autophagy, and G0/G1 phase cell cycle arrest in vitro and in vivo.

细胞凋亡 细胞周期 自噬 体内 细胞周期检查点 流式细胞术 细胞生长 生物 PI3K/AKT/mTOR通路 活力测定 癌症研究 G1期 细胞 分子生物学 细胞生物学 化学 生物化学 生物技术
作者
Xinghan Liu,Yujun Xu,Yi Li,Yuchen Pan,Zhiheng Sun,Shuli Zhao,Yayi Hou
出处
期刊:PubMed 卷期号:12 (6): 2675-2684 被引量:12
标识
摘要

Although previous studies have found that Ganoderma lucidum extracts have the ability to directly resist tumor proliferation and reduce metastasis and invasion, the effect of the extracts of Ganoderma lucidum fruiting body (GLE) on cancer is not clarified. This study intends to investigate the anticancer role of GLE on HCT116 colorectal cancer cells in vitro and in vivo. The effects of GLE on the proliferation, apoptosis, autophagy and cell cycle arrest of HCT116 cells were detected by cell counting kit-8 (CCK-8), flow cytometry, electron microscope, quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay. Xenografted mouse models were used to evaluate the tumor growth inhibition effect of GLE in vivo. GLE could significantly inhibit the viability of four tumor cell lines (A549, SW1990, SKOV3 and HCT116) and HCT116 cells were more sensitive to GLE treatment with a half inhibitory concentration of 106 µg/mL. GLE treatment induced apoptosis of HCT116 cells by downregulating of the ratio of Bcl-2 to Bax and increasing cleaved caspase-3 and poly ADP-ribose polymerase (PARP) protein expression. Autophagy of HCT116 cells also increased after GLE treatment, as shown by observation of autophagosomes formation and altered protein expressions in the mTOR pathway. In addition, GLE treatment led to G0/G1 cell cycle arrest as evidenced by flow cytometry analysis and changes in cell-cycle-related gene expressions at the mRNA levels. Of note, in vivo evaluation indicated that GLE significantly inhibited tumor weight and tumor volume and decreased Ki67 expression. In summary, GLE has potential to be developed as an anticancer agent against colorectal cancer, and further evaluation is needed.

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