UDP-葡萄糖神经酰胺糖基转移酶通过调节 PI3K/AKT 通路促进宫颈癌细胞的增殖和糖酵解。
UDP-Glucose Ceramide Glycosyltransferase Contributes to the Proliferation and Glycolysis of Cervical Cancer Cells by Regulating the PI3K/AKT Pathway.
机构信息
Department of Obstetrics and Gynecology, Hangzhou Ninth People's Hospital, Hangzhou, Zhejiang, China.
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
出版信息
Ann Clin Lab Sci. 2021 Sep;51(5):663-669.
OBJECTIVE
UDP-glucose ceramide glycosyltransferase (UGCG), a critical enzyme for the synthesis of glucosylceramide, is implicated in various cellular processes. Over-expressed UGCG in several cancer types has been shown to be related to pro-cancerous processes, including cell proliferation, invasion, and multidrug resistance. However, the role of UGCG in cervical cancer remains largely unknown.
METHODS
The expression levels of UGCG in cervical cancer tissues and cells were detected by Western blot and qRT-PCR. Colony formation and MTT assays were performed to assess cell proliferation and viability. Cellular glucose and lactate consumption and ATP production were investigated by commercial kits.
RESULTS
UGCG was elevated in both the cervical cancer tissues and cells. siRNA-mediated down-regulation of UGCG repressed the cell proliferation of cervical cancer and reduced cell viability. Knockdown of UGCG suppressed the glycolytic activity of cervical cancer cells, with a decrease in cellular glucose consumption and lactate and ATP production. Moreover, the knockdown of UGCG sensitized cervical cancer cells to cisplatin. The protein expressions of PI3K and AKT phosphorylation were reduced in cervical cancer cells with silenced UGCG.
CONCLUSION
The knockdown of UGCG exerted an anti-tumor effect against cervical cancer through the inactivation of the PI3K/AKT pathway.
目的
UDP-葡萄糖神经酰胺糖基转移酶（UGCG）是神经酰胺合成的关键酶，参与多种细胞过程。几种癌症类型中过表达的 UGCG 与致癌过程有关，包括细胞增殖、侵袭和多药耐药。然而，UGCG 在宫颈癌中的作用在很大程度上尚不清楚。
方法
通过 Western blot 和 qRT-PCR 检测宫颈癌组织和细胞中 UGCG 的表达水平。通过集落形成和 MTT 分析评估细胞增殖和活力。通过商业试剂盒研究细胞葡萄糖和乳酸消耗以及 ATP 产生。
结果
UGCG 在宫颈癌组织和细胞中均升高。siRNA 介导的 UGCG 下调抑制了宫颈癌的细胞增殖并降低了细胞活力。UGCG 的敲低抑制了宫颈癌细胞的糖酵解活性，导致细胞葡萄糖消耗、乳酸和 ATP 产生减少。此外，UGCG 的敲低使宫颈癌细胞对顺铂敏感。沉默 UGCG 的宫颈癌细胞中 PI3K 和 AKT 磷酸化的蛋白表达减少。
结论
通过抑制 PI3K/AKT 通路，UGCG 的敲低对宫颈癌发挥了抗肿瘤作用。
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