Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Department of Anesthesia, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Exp Cell Res. 2019 Dec 1;385(1):111605. doi: 10.1016/j.yexcr.2019.111605. Epub 2019 Sep 4.
Pancreatic cancer is one of the most aggressive and lethal malignancies and it is the eighth most common cause of death from cancer worldwide. The purpose of this study was to investigate the role of GSG2 (HASPIN) in the development and progression of pancreatic cancer.
GSG2 expression was detected by immunohistochemistry in tumor tissue samples, and by qRT-PCR and Western blot assay in human pancreatic cancer cell lines. Cell proliferation was evaluated by MTT assay. Giemsa staining was used for analyzing colony formation. Cell cycle and cell apoptosis were determined using Fluorescence activated Cells Sorting. Wound healing assay and transwell assay were applied for examining cell migration. The molecular mechanism was investigated by human apoptosis antibody array. Tumor-bearing animal model was constructed to verify the effects of GSG2 on pancreatic cancer in vivo.
GSG2 expression was upregulated in pancreatic cancer tissues and human pancreatic cancer cell lines: PANC-1 and SW1990. Higher expression of GSG2 in tumor samples was associated with poorer prognosis. GSG2 knockdown suppressed cell proliferation, colony formation, metastasis and promoted cell apoptosis, which was also verified in vivo. In addition, GSG2 knockdown blocked the cell cycle in G2. It was also found that downregulation of GSG2 inhibited Bcl-2, Bcl-w, cIAP, HSP60 and Livin expression as well as promoted IGFBP-6 expression.
This study revealed that GSG2 upregulation was associated with pancreatic cancer progression. GSG2 knockdown inhibited cell proliferation, colony formation and migration, blocked cell cycle at G2 phase, and induced cell apoptosis. Therefore, GSG2 might serve as a potential therapeutic target for pancreatic cancer therapy and a market for prognosis.
胰腺癌是最具侵袭性和致命性的恶性肿瘤之一，也是全球第八大常见癌症死亡原因。本研究旨在探讨 GSG2（HASPIN）在胰腺癌发生发展中的作用。
采用免疫组织化学法检测肿瘤组织标本中 GSG2 的表达，采用 qRT-PCR 和 Western blot 法检测人胰腺癌细胞系中 GSG2 的表达。用 MTT 法检测细胞增殖。用吉姆萨染色法分析集落形成。用荧光激活细胞分选法检测细胞周期和细胞凋亡。用划痕愈合实验和 Transwell 实验检测细胞迁移。用人凋亡抗体阵列研究分子机制。构建荷瘤动物模型验证 GSG2 对胰腺癌的体内作用。
GSG2 在胰腺癌组织和人胰腺癌细胞系 PANC-1 和 SW1990 中表达上调：肿瘤组织中 GSG2 表达上调与预后不良相关。GSG2 敲低抑制细胞增殖、集落形成、转移，并促进细胞凋亡，在体内也得到了验证。此外，GSG2 敲低阻滞细胞周期于 G2 期。还发现下调 GSG2 抑制 Bcl-2、Bcl-w、cIAP、HSP60 和 Livin 表达，促进 IGFBP-6 表达。
本研究表明 GSG2 上调与胰腺癌进展相关。GSG2 敲低抑制细胞增殖、集落形成和迁移，阻滞细胞周期于 G2 期，诱导细胞凋亡。因此，GSG2 可能成为胰腺癌治疗和预后的潜在治疗靶点。
