Therapeutic significance of elevated tissue transglutaminase expression in pancreatic cancer

被引：83

作者：

Verma, Arnit ^{[1
]}

Guha, Sushovan ^{[2
]}

Diagaradjane, Parmeswaran ^{[3
]}

Kunnumakkara, Ajaikumar B. ^{[1
]}

Sanguino, Angela M. ^{[1
]}

Lopez-Berestein, Gabriel ^{[1
]}

Sood, Anil K. ^{[4
,5
]}

Aggarwal, Bharat B. ^{[1
]}

Krishnan, Sunil ^{[3
]}

Gelovani, Juri G. ^{[6
]}

Mehta, Kapil ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77030 USA

来源：

CLINICAL CANCER RESEARCH | 2008年 / 14卷 / 08期

关键词：

D O I：

10.1158/1078-0432.CCR-07-4529

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: Tissue transglutaminase (TG2) is a multifunctional protein that is implicated in development of drug resistance and metastasis. Therefore, we examined therapeutic targeting of TG2 for inhibiting growth and metastasis of in vivo growing pancreatic ductal adenocarcinoma (PDAC) in nude mice. Experimental Design: We implanted Panc-28 pancreatic cancer cells to induce orthotopic PDAC tumors in nude mice and determined the efficacy of liposomal TG 2 small interfering RNA (si RNA) either alone or in combination with gemcitabine. Results: We show that down-regulation of endogenous TG2 by siRNA could effectively block the growth of PDAC. Moreover, down-regulation of TG2 significantly enhanced the therapeutic efficacy of gemcitabine against PDAC and inhibited metastatic spread of the disease. The antitumor activity was related to inhibition of proliferation, angiogenesis, and Akt phosphorylation. Conclusion: siRNA-mediated down-regulation of TG2 represents a promising therapeutic approach for improved treatment of PDAC.

引用

页码：2476 / 2483

页数：8

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