The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
The First Department of General Surgery, Cangzhou Central Hospital, Cangzhou, China.
Neoplasma. 2020 Mar;67(2):277-285. doi: 10.4149/neo_2019_190404N295. Epub 2019 Dec 17.
Pancreatic cancer (PC) is a complex and multifactorial human malignancy with a low survival rate. Tumor protein D52 (TPD52) was abnormally expressed in several cancers and participated in tumorigenesis. However, the oncogenic effect of TPD52 on PC remains unknown. In the present study, after transfecting AsPC-1 and PANC-1 cells with NC or sh-TPD52, the CCK-8 assay, Hoechst staining, western blot, transwell assay, flow cytometry were used to examine the cell proliferation, migration, invasion and apoptosis. qRT-PCR results confirmed that the expression of TPD52 was significantly increased in PC cells, especially AsPC-1 and PANC-1 cells. The present study revealed that silencing of TPD52 significantly suppressed the proliferation, migration and invasion, but induced apoptosis of AsPC-1 and PANC-1 cells in vitro by dephosphorylating Akt at Ser473. Conversely, SC79, an Akt activator, could partially reverse the anti-metastatic effects of sh-TPD52, accompanied by the reactivating of Akt pathway. Additional in vivo studies are warranted to elucidate that knockdown of TPD52 could inhibit tumor growth in PC mice models. These findings suggested that TPD52 might be a novel therapeutic target for PC treatment.
胰腺癌（PC）是一种复杂的多因素人类恶性肿瘤，其生存率较低。肿瘤蛋白 D52（TPD52）在几种癌症中异常表达，并参与肿瘤发生。然而，TPD52 对 PC 的致癌作用尚不清楚。在本研究中，用 NC 或 sh-TPD52 转染 AsPC-1 和 PANC-1 细胞后，使用 CCK-8 测定法、Hoechst 染色、western blot、transwell 测定法和流式细胞术来检测细胞增殖、迁移、侵袭和凋亡。qRT-PCR 结果证实 TPD52 的表达在 PC 细胞中显著增加，特别是在 AsPC-1 和 PANC-1 细胞中。本研究表明，沉默 TPD52 可通过使 Akt 在 Ser473 去磷酸化，显著抑制 AsPC-1 和 PANC-1 细胞的体外增殖、迁移和侵袭，但诱导其凋亡。相反，Akt 激活剂 SC79 可部分逆转 sh-TPD52 的抗转移作用，同时激活 Akt 通路。需要进一步的体内研究来阐明敲低 TPD52 可抑制 PC 小鼠模型中的肿瘤生长。这些发现表明 TPD52 可能是治疗 PC 的新的治疗靶点。
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