Cancer Research institute, MD Anderson Cancer Center Orlando, 6900 Lake Nona Blvd, Orlando, FL 32827, USA.
Curr Med Chem. 2012;19(22):3779-86. doi: 10.2174/092986712801661077.
Pancreatic cancer is an aggressive malignancy with poor prognosis. Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in the United States. Due to the aggressive nature of this malignancy, there is a serious concern for identifying effective targets, and adopting novel strategies for therapy. Members of the Specificity Protein (Sp) family of transcription factors, Sp1, Sp3, and Sp4 regulate the expression of a number of genes associated with cancer cell proliferation, differentiation, and metastasis. Sp1 levels are upregulated in pancreatic cancer cell lines, and surgically resected human pancreatic adenocarcinoma. Sp1 overexpression in tumor tissues is associated with aggressive disease, poor prognosis and inversely correlated with survival. Sp1 is also known to affect angiogenesis by regulating the expression of vascular endothelial growth factor and its receptors. Results from clinical studies suggest Sp1 as new biomarker to identify aggressive pancreatic ductal adenocarcinoma. The pharmacological inhibition of Sp1 using agents such as celecoxib, mithramycin, curcumin, and tolfenamic acid has showed promising results in pre-clinical studies and demonstrated Sp transcription factors as potential targets for pancreatic cancer therapy. This review summarizes studies showing the association of Sp proteins with this malignancy, with a special emphasis on pre-clinical studies that tested strategies to target Sp transcription factors for inhibiting human pancreatic cancer cell proliferation and tumor growth in laboratory animals. The results showed remarkable efficacy and suggest that such approaches have the potential for high success in developing clinically relevant strategies for treating pancreatic cancer.
胰腺癌是一种预后不良的侵袭性恶性肿瘤。胰腺腺癌是美国癌症相关死亡的主要原因之一。由于这种恶性肿瘤的侵袭性，人们非常关注识别有效的靶点，并采用新的治疗策略。特异性蛋白（Sp）家族的转录因子成员 Sp1、Sp3 和 Sp4 调节与癌细胞增殖、分化和转移相关的许多基因的表达。Sp1 在胰腺癌细胞系和手术切除的人类胰腺腺癌中上调。肿瘤组织中 Sp1 的过表达与侵袭性疾病、预后不良相关，与生存呈负相关。Sp1 还通过调节血管内皮生长因子及其受体的表达来影响血管生成。临床研究结果表明 Sp1 可作为识别侵袭性胰腺导管腺癌的新生物标志物。使用塞来昔布、米托霉素、姜黄素和托芬酸等药物抑制 Sp1 的药理作用在临床前研究中显示出了有希望的结果，并证明 Sp 转录因子是胰腺癌治疗的潜在靶点。本文综述了表明 Sp 蛋白与这种恶性肿瘤相关的研究，特别强调了测试针对 Sp 转录因子的策略以抑制人类胰腺癌细胞增殖和在实验动物中肿瘤生长的临床前研究。结果表明其具有显著的疗效，表明这些方法有可能成功开发出治疗胰腺癌的临床相关策略。
