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目的探讨Tiam1(T lymphoma invasion and metastasis 1)基因转染对结直肠癌细胞增殖、转移能力的影响。方法采用裸鼠皮下接种结直肠癌细胞的方法观察Tiam1基因对结直肠癌细胞体内增殖能力的影响,利用外科原位移植技术观察Tiam1对体内增殖、转移能力的影响。结果接种HT29/Tiam1细胞(转染Tiam1基因)的裸鼠皮下肿瘤生长明显加快,肿瘤体积自皮下注射后的第7天起与接种HT29/mock细胞(转染对照)的裸鼠皮下肿瘤比差异有统计学意义,接种HT29/Tiam1细胞的裸鼠皮下肿瘤第20天的平均体积是接种HT29/mock细胞组的2.5倍。进行结直肠癌细胞外科原位移植6周后,接种HT29/Tiam1细胞的裸鼠结肠原位肿瘤重量明显犬于接种HT29/mock细胞的裸鼠(t=-14.916,P<0.01)。采用外科原位移植的方法比较HT29/mock和HT29/Tiam1细胞的体内转移能力。在HT29/Tiam1细胞组,7只裸鼠全都发生了腹腔转移,4只发生了肝转移,其中有1只裸鼠发生了广泛转移,包括脾、肺及淋巴结等转移。在HT29/mock细胞组,7只中只有2只裸鼠发生了腹腔转移,没有一只裸鼠发生远处转移。结论Tiam1基因是结直肠癌增殖、转移的促进基因,Tiam1表达可作为结直肠癌增殖、转移过程中一个有价值的指标。
Objective To investigate the effect of Tiam1 gene transfection on the proliferation and metastasis of colorectal cancer cells. Methods The effects of Tiam1 gene on the proliferation of colorectal cancer cells in vivo were observed by subcutaneous inoculation of colorectal cancer cells in nude mice. The effects of Tiam1 on the proliferation and metastasis of colorectal cancer cells were observed by in situ orthotopic implantation. Results The growth of subcutaneous tumors in nude mice bearing HT29 / Tiam1 cells transfected with Tiam1 gene was significantly accelerated. The tumor volume was significantly lower than that of nude mice bearing HT29 / mock cells (transfection control) from the 7th day after subcutaneous injection Statistically, the mean volume of subcutaneous tumors of nude mice vaccinated with HT29 / Tiam1 cells on day 20 was 2.5 times more than that of HT29 / mock cells. After 6 weeks of orthotopic colorectal cancer cell transplantation in situ, the in situ colon tumor weight of nude mice bearing HT29 / Tiam1 cells was significantly higher than that of nude mice bearing HT29 / mock cells (t = -14.916, P <0.01). Survival in vivo of HT29 / mock and HT29 / Tiam1 cells was compared using surgical orthotopic transplantation. In the HT29 / Tiam1 cell group, all seven nude mice had peritoneal metastasis and four had liver metastases. One of them had extensive metastasis, including spleen, lung and lymph node metastasis. In the HT29 / mock cell group, only two of the seven nude mice had peritoneal metastases, and none of the nude mice had distant metastases. Conclusion Tiam1 gene is a promoter of proliferation and metastasis of colorectal cancer. Tiam1 expression may be a valuable index in the process of proliferation and metastasis of colorectal cancer.