生物钟基因Period2对卵巢癌裸鼠移植瘤生长抑制作用的机制研究

Research on the mechanism of period2 on the growth inhibition of human ovarian cancer xenografts in nude mice

目的:探讨生物钟基因Period2对卵巢癌裸鼠移植瘤生长抑制的作用机制。方法:采用卵巢癌SKVO3细胞株构建裸鼠卵巢癌移植瘤,利用基因转染技术外源性导入重组基因质粒Period2。采用Real-time PCR法和Western bolt法检测移植瘤中Period2表达,治疗期间测量移植瘤体积。治疗后2周处死裸鼠,称取瘤重,采用Real-time PCR和Western blot法检测肿瘤组织中Bcl-2和Bax基因的表达。结果:外源性导入Period2基因在裸鼠移植瘤肿瘤组织中成功稳定表达。与对照组比较,Period2基因过表达组的肿瘤生长速度减慢,肿瘤体积和重量降低,抑瘤率升高,凋亡基因Bax表达明显升高,凋亡抑制基因Bcl-2表达明显降低,差异均有统计学意义(P<0.05)。结论:Period2可能通过下调肿瘤凋亡抑制基因Bcl-2,促进凋亡基因Bax表达,促进肿瘤细胞凋亡,从而抑制卵巢癌的生长转移,发挥抑瘤作用。

Objective： To investigate the mechanism of biological clock gene Period2 on the growth inhibition of human ovarian cancer xenografts in nude mice. Methods： Construction of ovarian cancer xenograft in nude mice with ovarian cancer SKVO3 cell. By using gene transfection technique,the recombinant gene Period2 was introduced into the tumor tissue. The expression of Period2 was detected by Real-time PCR and Western blot methods. The animals were sacrificed in two weeks after treatment and measured the weight of the tumor. The volume and weight of the tumor were measured during intervention. Real-time PCR and Western blot methods were used to detect the expressions changes of B cell lymphoma-2 gene（ Bcl-2） and Bcl-2 related X protein（ Bax） gene in tumor tissues. Results： Period2 gene was successfully transfected and expressed in the tumor tissues of nude mice. Compared with the other two groups,the tumor growth rate of Period2 overexpression group was slowed,tumor volume and weight was reduced,tumor inhibition rate was increased,the expression of apoptosis gene Bax was increased,and the expression of apoptosis inhibition gene Bcl-2 was decreased. The difference was statistically significant compared with the other two groups（ P 〈0. 05）. Conclusions：Period2 may promote tumor cell apoptosis by inhibiting the expression of apoptosis inhibition gene Bcl-2 and promoting the expression of apoptosis related gene Bax. So it can inhibit the growth and metastasis of ovarian cancer,and play a role in tumor suppression.