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沉默 GPR81 联合顺铂刺激对下咽鳞癌细胞生物学功能的影响。

Effects of GPR81 silencing combined with cisplatin stimulation on biological function in hypopharyngeal squamous cell carcinoma.

机构信息

E.N.T. Department, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.

出版信息

Mol Med Rep. 2020 Sep;22(3):1727-1736. doi: 10.3892/mmr.2020.11255. Epub 2020 Jun 18.

DOI:10.3892/mmr.2020.11255
PMID:32582969
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7411294/
Abstract

Hypopharyngeal squamous cell carcinoma (HSCC) is a malignant tumor found in the head and neck region. Lactate receptor 1, also known as G protein‑coupled receptor81 (GPR81), has been reported to play a vital role in cancer growth and metabolism. However, the function of GPR81 in HSCC remains largely unknown. The present study investigated the effect of GPR81 on cell survival and GPR81‑mediated energy metabolism under cisplatin treatment in HSCC. GPR81 knockdown reduced the proliferation and invasion of the human HSCC cell line FaDu. Furthermore, GPR81 silencing combined with cisplatin treatment increased the expression of translocase of outer mitochondrial membrane 20 at the mRNA and protein levels (P<0.05). mRNA and protein expression of phosphofructokinase 1 in mRNA appeared to be downregulated in GPR81 knockdown FaDu cells treated with cisplatin, although this was not statistically significant. GPR81 silencing and cisplatin challenge showed no significant upregulation compared with the control, but significant downregulation in mRNA and protein levels compared with the shRNA‑scramble group. Apoptosis was measured by flow cytometry with annexin V and 7‑aminoactinomycin D. GPR81 silencing and cisplatin led to an increased apoptotic rate. Moreover, absence of GPR81 combined with cisplatin exposure increased caspase‑3 expression and decreased Bcl‑2 levels. The results of the present study suggested that GPR81 and cisplatin sensitivity played an important role in HSCC growth and metabolism.

摘要

下咽鳞状细胞癌(HSCC)是一种发生在头颈部的恶性肿瘤。乳酸受体 1,也称为 G 蛋白偶联受体 81(GPR81),据报道在癌症生长和代谢中发挥着重要作用。然而,GPR81 在 HSCC 中的功能仍知之甚少。本研究探讨了 GPR81 在 HSCC 中顺铂治疗下对细胞存活和 GPR81 介导的能量代谢的影响。GPR81 敲低减少了人 HSCC 细胞系 FaDu 的增殖和侵袭。此外,GPR81 沉默联合顺铂处理增加了外膜线粒体转位酶 20 在 mRNA 和蛋白质水平上的表达(P<0.05)。在 GPR81 敲低 FaDu 细胞中用顺铂处理后,磷酸果糖激酶 1 的 mRNA 和蛋白表达似乎下调,但无统计学意义。与对照组相比,GPR81 沉默和顺铂挑战均未显著上调,但与 shRNA 乱序组相比,mRNA 和蛋白水平显著下调。用 Annexin V 和 7-氨基放线菌素 D 通过流式细胞术测量细胞凋亡。GPR81 沉默和顺铂导致凋亡率增加。此外,缺乏 GPR81 结合顺铂暴露增加了 caspase-3 的表达并降低了 Bcl-2 水平。本研究的结果表明,GPR81 和顺铂敏感性在 HSCC 生长和代谢中发挥着重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a98/7411294/31e507412620/MMR-22-03-1727-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a98/7411294/e102a2977705/MMR-22-03-1727-g00.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a98/7411294/9d3a815647f3/MMR-22-03-1727-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a98/7411294/de0f07b80e07/MMR-22-03-1727-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a98/7411294/ec707b7ec1ef/MMR-22-03-1727-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a98/7411294/31e507412620/MMR-22-03-1727-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a98/7411294/e102a2977705/MMR-22-03-1727-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a98/7411294/0c0cafd9a740/MMR-22-03-1727-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a98/7411294/9d3a815647f3/MMR-22-03-1727-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a98/7411294/de0f07b80e07/MMR-22-03-1727-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a98/7411294/ec707b7ec1ef/MMR-22-03-1727-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a98/7411294/31e507412620/MMR-22-03-1727-g05.jpg

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