肝细胞生长因子拮抗剂NK4对裸鼠体内人宫颈癌种植瘤生长的影响

Effect of NK4 on tumor growth of human cervical cancer xenograft in nude mice

目的通过建立裸鼠皮下肿瘤生长模型,研究肝细胞生长因子(HGF)拮抗剂NK4在裸鼠体内对人宫颈癌细胞的生长抑制作用。方法 NK4和荧光霉素表达质粒分别稳定转染至人宫颈癌细胞CaSki;应用Western blot检测NK4在细胞培养基中的分泌表达情况;检测3组肿瘤细胞(CaSki、CaSki/LUC和CaSki/NK4)体外生长速度;种植3组肿瘤细胞至裸鼠皮下,比较其在裸鼠体内的生长速度。结果在CaSki/NK4培养基中有NK4蛋白表达,对照(CaSki和CaSki/LUC)细胞中无表达。3组肿瘤细胞体外生长曲线无统计学差异(P>0.05)。1周后CaSki/NK4细胞接种的肿瘤生长缓慢,CaSki和CaSki/LUC细胞接种的肿瘤生长迅速,两组比较P<0.05。结论本研究观察到在裸鼠体内NK4能抑制宫颈癌种植瘤的生长,因此NK4是一个潜在的治疗宫颈癌的新策略。

Objective To clarify the antitumor activity of antagonist of hepatocyte growth factor （HGF） NK4 in cervi- cal cancer by checking the tumor growth of human cervical cancer xenograft in nude mice. Methods CaSki cells were sta- ble transfected with NK4 or luciferase expression plasmids. Western blot analysis was used to detect NK4 expression in the supernatants of CaSki, CaSki/LUC and CaSki/NK4 cells. Cell growth curves were performed using MTI＂ kit. Subcutaneous tumor growth curve were performed according to the xenograft tumor volume among the three groups. Results NK4 was de- tected in the supernatant of CaSki/NK4 cells but was not detected in control （ CaSki or CaSki/LUC） cells. There was no intergroup difference in doubling time in vitro （ P 〉 0.05 ）. The subcutaneous tumor volume was significantly larger than that in the control groups （ P 〈 0.05 ）. Conclusions NK4 can be expressed by established CaSki/NK4 cells. Although NK4 has no effect on cell proliferation in CaSki cells in vitro, NK4 can inhibit cervical cancer growth in nude mice. These findings suggest NK4 is a potential gene therapeutic strategy to human cervical cancer.