Polysaccharides from sporoderm-removed spores of Ganoderma lucidum induce apoptosis in human gastric cancer cells via disruption of autophagic flux.

Polysaccharides from sporoderm-removed spores of Ganoderma lucidum induce apoptosis in human gastric cancer cells via disruption of autophagic flux.
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DOI:
10.3892/ol.2021.12686
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发表时间:
2021-05
期刊:
影响因子:
2.9
通讯作者:
Wang X
Wang X
中科院分区:
医学4区
文献类型:
--
作者:
Zhong J;Fang L;Chen R;Xu J;Guo D;Guo C;Guo C;Chen J;Chen C;Wang X

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灵芝(Ganoderma lucidum,G.灵芝)多糖(BSGLP)已被证明在几种类型的癌症中抑制致癌作用。然而,据我们所知,从新开发的去除孢子壁的G. lucidum(RSGLP)尚未评估。本研究首次比较了RSGLP和BSGLP对三种胃癌细胞系的抗癌作用,发现RSGLP比BSGLP更有效地降低胃癌细胞的活力。RSGLP可明显诱导AGS细胞凋亡,并下调Bcl-2和caspase-3原表达水平,上调切割PARP。此外,RSGLP增加LC 3-II和p62表达,指示AGS细胞中自噬的诱导和自噬通量的破坏。这些结果通过用晚期自噬抑制剂氯喹或早期自噬诱导剂雷帕霉素联合处理AGS细胞得到进一步验证。腺病毒转染mRFP-GFP-LC 3进一步证实了RSGLP抑制AGS细胞的自噬通量。最后,本研究表明,RSGLP诱导的自噬和自噬通量的破坏是,至少部分地,负责RSGLP诱导的AGS细胞凋亡。本研究的结果首次证明,RSGLP在抑制胃癌细胞活力方面比BSGLP更有效,并且RSGLP可能作为胃癌管理中有希望的自噬抑制剂。
The sporoderm-broken spores of Ganoderma lucidum (G. lucidum) polysaccharide (BSGLP) have been demonstrated to inhibit carcinogenesis in several types of cancer. However, to the best of our knowledge, the anticancer effects of polysaccharides extracted from the newly developed sporoderm-removed spores of G. lucidum (RSGLP) have not been assessed. The present study first compared the anticancer effects of RSGLP and BSGLP in three gastric cancer cell lines and it was found that RSGLP was more potent than BSGLP in decreasing gastric cancer cell viability. RSGLP significantly induced apoptosis in AGS cells, accompanied by downregulation of Bcl-2 and pro-caspase-3 expression levels, and upregulation of cleaved-PARP. Furthermore, RSGLP increased LC3-II and p62 expression, indicative of induction of autophagy and disruption of autophagic flux in AGS cells. These results were further verified by combined treatment of AGS cells with the late-stage autophagy inhibitor chloroquine, or early-stage autophagy inducer rapamycin. Adenoviral transfection with mRFP-GFP-LC3 further confirmed that autophagic flux was inhibited by RSGLP in AGS cells. Finally, the present study demonstrated that the RSGLP-induced autophagy and disruption of autophagic flux disruption was, at least in part, responsible for RSGLP-induced apoptosis in AGS cells. The results of the present study demonstrated for the first time that RSGLP is more effective than BSGLP in inhibiting gastric cancer cell viability, and RSGLP may serve as a promising autophagy inhibitor in the management of gastric cancer.
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