IGF-Ⅰ受体反义寡核苷酸对胰腺癌生长的抑制作用

Growth inhibition of pancreatic cancer by antisense oligonucleotide against the insulin like growth factor Ⅰ receptor

目的 观察 Ｉ Ｇ ＦⅠ受体反义寡核苷酸对胰腺癌细胞生长的抑制作用，为反义核酸疗法在胰腺癌外科综合治疗提供依据。 方法 以免疫组织化学 Ｓ Ｐ法检测 Ｉ Ｇ Ｆ１ 受体在体外培养的胰腺癌细胞系 Ｓ Ｗ１９９０ 的表达；用脂质体包裹合成的 Ｉ Ｇ ＦⅠ受体反义寡核苷酸（ Ａ Ｓ Ｏ Ｎ） 与 Ｓ Ｗ１９９０ 细胞共培养，并接种于裸鼠体内，观察细胞增殖情况。 结果 Ｓ Ｗ１９９０ 细胞高表达 Ｉ Ｇ ＦⅠ受体，经上述处理细胞增殖抑制率达到８００ ％ ； Ｉ Ｇ ＦⅠ受体表达抑制率为８３９ ％ 。对照组裸鼠体内全部出瘤（１０／１０ ，１００ ％ ） ，处理组出瘤率为２０ ％ （２／１０） ，二者差异有显著意义（ Ｐ＜ ００１） 。 结论 Ｉ Ｇ ＦⅠ受体反义寡核苷酸可显著抑制胰腺癌细胞系 Ｓ Ｗ１９９０ 在体外及体内的生长，其作用是经抑制受体表达所介导。

Objective The insulin like growth factor 1 receptor (IGF ⅠR) plays a crucial role in cell proliferation and tumorigenicity. It is reasonable to assume that the antisense oligonucleotide (ASON) leading to a reduction in the expression of IGF ⅠR may cause inhibition of proliferation and tumorigenicity. This study was designed to test our hypothesis.Methods The expression of IGF Ⅰ recepeor was examined by immunocytochemical SP method in human pancreatic cancer cell lines SW 1990. SW 1990 cells were exposed to a liposomal ASON complementary to IGF ⅠR encorded mRNA. Results It was showed that the liposomal ASON significantly inhibited the growth of SW 1990 cells by 80 0% and also led to dramatic inhibition of IGF ⅠR expression by 83 6% while the liposome alone had no inhibitory effect on IGF ⅠR Inhibition (80 0%,2/10) of tumorigenesis in nude mice was also evident when pancreatic cancer SW 1990 cells were incubated with liposomal ASON.Conclusions These results suggested that this antisense strategy against IGF Ⅰ receptor may prove to be useful as a therapeutic approach in pancreatic cancer therapy.