Therapeutic significance of elevated tissue transglutaminase expression in pancreatic cancer
Therapeutic significance of elevated tissue transglutaminase expression in pancreatic cancer
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DOI：
10.1158/1078-0432.ccr-07-4529
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发表时间：
2008-04-15
影响因子：
11.5
通讯作者：
Mehta, Kapil
中科院分区：
文献类型：
--
作者：
Verma, Arnit;Guha, Sushovan;Mehta, Kapil
目的：组织转氨酶（TG 2）是一种多功能蛋白，与肿瘤的耐药性和转移有关。因此，我们研究了TG 2抑制裸鼠体内生长的胰腺导管腺癌（PDAC）的生长和转移的治疗靶向。实验设计：我们将Panc-28胰腺癌细胞植入裸鼠体内以诱导原位PDAC肿瘤，并确定单独或与吉西他滨组合的脂质体TG 2小干扰RNA（siRNA）的功效。我们发现，通过siRNA下调内源性TG 2可以有效地阻断PDAC的生长。此外，TG 2的下调显着增强了吉西他滨对PDAC的治疗效果，并抑制了疾病的转移性传播。抗肿瘤活性与抑制增殖、血管生成和Akt磷酸化有关。结论：siRNA介导的TG 2下调是改善PDAC治疗的一种有前景的治疗方法。
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.