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肺腺癌中 PKCζ、MMP-2 和 MMP-9 的表达及其与转移表型的关系。

PKCζ, MMP‑2 and MMP‑9 expression in lung adenocarcinoma and association with a metastatic phenotype.

机构信息

Department of Pathology, Second People's Hospital of Weifang, Weifang, Shandong 261041, P.R. China.

Department of Dentistry, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China.

出版信息

Mol Med Rep. 2017 Dec;16(6):8301-8306. doi: 10.3892/mmr.2017.7634. Epub 2017 Sep 26.

Abstract

The aim of the present study was to investigate protein kinase C ζ type (PKCζ), matrix metalloproteinase (MMP)‑2 and MMP‑9 expression in lung adenocarcinoma and to define their association with in vitro invasion and metastatic capacity. PKCζ, MMP‑2 and MMP‑9 expression was assessed by immunohistochemistry in 110 cases of lung adenocarcinoma. PKCζ small interfering (si)RNA was transfected into A549 cells, and western blotting was used to confirm PKCζ‑knockdown in transfected cells and to measure MMP‑2 and MMP‑9 levels. A Transwell invasion assay was used to detect in vitro invasive capacity. The rates of positive PKCζ, MMP‑2 and MMP‑9 staining in lung adenocarcinoma tissues were 52.73, 55.45 and 61.82%, respectively. PKCζ expression was increased in malignant tissues compared with adjacent normal lung tissues and was associated with lymph node metastasis (P<0.05), although it was not associated with any other clinicopathological parameters, including sex, age, tumor size, smoking status or distant metastases (all P>0.05). PKCζ, MMP‑2 and MMP‑9 expression was markedly decreased in siPKCζ‑treated A549 cells, which exhibited a significantly decreased invasive capacity in the Transwell invasion assay (P<0.05). In conclusion, PKCζ promoted lung adenocarcinoma invasion and metastasis, and its expression was associated with MMP‑2 and MMP‑9 expression. PKCζ may be a potential target for gene therapy in lung adenocarcinoma.

摘要

本研究旨在探讨蛋白激酶 C ζ 型(PKCζ)、基质金属蛋白酶(MMP)-2 和 MMP-9 在肺腺癌中的表达,并确定它们与体外侵袭和转移能力的关系。采用免疫组织化学法检测 110 例肺腺癌组织中 PKCζ、MMP-2 和 MMP-9 的表达。用 PKCζ 小干扰(si)RNA 转染 A549 细胞,用 Western blot 验证转染细胞中 PKCζ 的敲低,并测量 MMP-2 和 MMP-9 水平。用 Transwell 侵袭实验检测体外侵袭能力。肺腺癌组织中 PKCζ、MMP-2 和 MMP-9 染色的阳性率分别为 52.73%、55.45%和 61.82%。与相邻正常肺组织相比,恶性组织中 PKCζ 的表达增加,且与淋巴结转移相关(P<0.05),但与其他临床病理参数(包括性别、年龄、肿瘤大小、吸烟状况或远处转移)均无相关性(均 P>0.05)。在 siPKCζ 处理的 A549 细胞中,PKCζ、MMP-2 和 MMP-9 的表达明显降低,Transwell 侵袭实验显示其侵袭能力显著降低(P<0.05)。综上所述,PKCζ 促进肺腺癌侵袭和转移,其表达与 MMP-2 和 MMP-9 的表达相关。PKCζ 可能是肺腺癌基因治疗的潜在靶点。

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