Peritumoral injection of adenovirus vector expressing NK4 combined with gemcitabine treatment suppresses growth and metastasis of human pancreatic cancer cells implanted orthotopically in nude mice and prolongs survival
Peritumoral injection of adenovirus vector expressing NK4 combined with gemcitabine treatment suppresses growth and metastasis of human pancreatic cancer cells implanted orthotopically in nude mice and prolongs survival
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DOI：
10.1038/sj.cgt.7700921
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发表时间：
2006-05
影响因子：
6.4
通讯作者：
Y. Ogura;K. Mizumoto;E. Nagai;M. Murakami;N. Inadome;M. Saimura;K. Matsumoto;T. Nakamura;M. Maemondo;T. Nukiwa;M. Tanaka
中科院分区：
文献类型：
--
作者：
Y. Ogura;K. Mizumoto;E. Nagai;M. Murakami;N. Inadome;M. Saimura;K. Matsumoto;T. Nakamura;M. Maemondo;T. Nukiwa;M. Tanaka
NK 4或表达NK 4的腺病毒载体（Ad-NK 4）具有肝细胞生长因子拮抗剂和血管生成抑制剂的双重功能，在肿瘤治疗中具有潜在的应用价值。本研究的目的是评估Ad-NK 4联合吉西他滨（GEM）治疗胰腺癌的疗效。体外实验表明，GEM具有较强的抗胰腺癌细胞增殖作用，Ad-NK 4具有较强的抗胰腺癌细胞侵袭作用。在体内实验中，将SUIT-2人胰腺癌细胞植入裸鼠胰腺中。通过在植入后第5天注射到胰腺的肿瘤周围区域中，然后每周ip注射GEM，用Ad-NK 4处理小鼠。在植入后第28天，胰腺肿瘤体积显著小于单独用Ad-LacZ、Ad-NK 4或单独用GEM治疗的小鼠。此外，联合治疗完全抑制腹膜播散和肝转移，导致生存率显着增加。原发性肿瘤的组织学和免疫组织化学分析表明，联合治疗抑制了细胞增殖和血管生成，导致高水平的细胞凋亡。这些结果表明，肿瘤周围注射Ad-NK 4加GEM是胰腺癌的有效联合治疗。
NK4 or adenovirus vector expressing NK4 (Ad-NK4) can act bifunctionally as a hepatocyte growth factor antagonist and angiogenesis inhibitor and has potential value in cancer therapy. The aim of this study was to evaluate the therapeutic efficacy of Ad-NK4 in combination with gemcitabine (GEM) against pancreatic cancer. In vitro study showed a strong antiproliferative effect of GEM and a potent anti-invasive effect of Ad-NK4 against pancreatic cancer cells. In in vivo experiments, SUIT-2 human pancreatic cancer cells were implanted into the pancreas of nude mice. Mice were treated with Ad-NK4 by injection into the peritumoral region of the pancreas on day 5 after implantation followed by weekly ip injections of GEM. On day 28 after implantation, pancreatic tumor volume was significantly smaller than that in mice treated with Ad-LacZ, Ad-NK4 alone, or GEM alone. Furthermore, combination therapy completely suppressed peritoneal dissemination and liver metastases, leading to significantly increased survival. Histologic and immunohistochemical assays of primary tumors indicated that combination therapy prohibited both cell proliferation and angiogenesis, resulting in high levels of apoptosis. These results suggest that peritumoral injection of Ad-NK4 plus GEM is a potent combination therapy for pancreatic cancer.