蛋白酪氨酸激酶2对人大肠癌细胞生长和肺转移能力的影响

Effects of proline-rich tyrosine kinase 2 on growth and hematogenous metastasis of human colorectal cancer cells

目的观察富含脯氨酸的蛋白酪氨酸激酶2（Pyk2）对人大肠癌细胞生长和肺转移能力的影响。方法利崩人大肠癌细胞株SW480，通过止义及反义eDNA稳定转染技术，分别构建Pyk2高表达和低表达的细胞SW480-Pyk2-和SW480-Pyk2-，并以未转染质粒和转染空质粒的SW480细胞作为对照。分别建辽裸鼠皮下种植瘤和肺转移模型。6周后，切取皮下种植瘤体并称重；切取肺转移标本，在显微镜下计数转移灶数目。结果Westernblot法证实Pyk2高表达、低表达及宅质粒细胞构建成功；SW480-Pyk2’组（MeanRank=6．19）皮下种植瘤质量明显低于SW480组（MeanRank=18．69）和SW480-Vector组（MeanRank=14．12），而SW480-PI，k2-组（MeanRank=27．00）日月显高于SW480组和SW480-vector组，差异有统计学意义（x2=20．646，P〈0．05）；SW480-Pyk2’组（MeanRank=6．62）肺转移灶数目明显少于SW480组（MeanRank=16．06）和SW480-veetor组（MeanRank=14．94），SW480-Pyk2组（MeanRank=28．38）肺转移灶数目明显多于SW480组和SW480-vector组，差异有统计学意义（x2=21．948，P〈0．05）；并且种植瘤质量和肺转移灶数与Pyk2的表达量均旱明显负相关（r=-0．776，-0．777，P〈0．05）。结论Pyk2在裸鼠体内能够抑制大肠痈细胞的生长和肺转移能力。

Objective To investigate the effects of the proline-rich tyrosine kinase 2 （ Pyk2 ） on the growth and the hematogenous metastasis of the human colorectal cancer SW480 cells. Methods SW480 cells were stably transfected with empty vector （pcDNA4-A） , vector containing Pyk2 ＋ or Pyk2 , respeclively. Cells from each group （SW480-Pyk2＋, SW480, SW480-vector and SW480-Pyk2 cells） were inoculated subcutaneously into g nude mice （ BALB/C nu/nu） respectively. Six weeks later, the sub- cutaneous tumors were harvested and weighed. Lungs were harvested 6 weeks after nude mice lung metasta- sis model was constructed. Then the lung metastatic amounts were counted by microscopy. Results The mass of the subcutaneous tumors in SW480-Pyk2 ＋ group （Mean Rank = 6. 19） was less than other groups （ SW480 18.69, SW480-vector 14. 12）, and that in SW480-Pyk2 group （ Mean Rank = 27.00） was more than other groups （X~ = 20. 646, P 〈 0. 05 ）. The lung metastatic amounts in SW480-Pyk2 ＋ group （ Mean Rank = 6.62） were the least, those in SW480-Pyk2- group （ Mean Rank = 28.38） were the most, and those in the remaining two groups （ SW480 16. 06, SW480-vector 14. 94） were moderate （X2 = 21. 948, P 〈 0. 05 ）. The expression of Pyk2 was highly negatively ton＇elated with the mass of the tumors and lung metastalie amounts （ r = - 0. 776, - 0. 777, P 〈 0.05 ）. Conclusion Pyk2 could inhibit the growth and the hmg metastasis of SW480 cells in vivoin nude mice.