在膠質瘤細胞中抑制FoxM1表達對其增殖和凋亡的影響初探.pdf

1、Gliomas, which accounts for more than 50％ as one of the primary tumors of the nervoussystem, is the most common primary central nervous system malignancies and also one of themost aggressive malignant tumors. There are a

2、bout 90,000 new patients per year inChina .With the in-depth understanding of the mechanism of glioma molecular biologypathogenesis, people gradually realized the occurrence and development of glioma is amulti-gene invol

3、vement, multi-link, multi-stage and multi-step complex process. The truthhas now been found that inactivation of functional tumor suppressor genes such as p53, Rb,P16 etc. and over-expression of nuclear transcription fac

4、tors such as FoxM1, MDM2, cdc2,VEGF, Survivin etc. can lead the tumor cells apoptosis suppressed and unlimited growth. Sowe need to find some of the key nuclear transcription factors, which can regulate multipledownstrea

5、m tumor-associated genes or the expression of apoptosis-related genes.
　　 FoxM1 is a proliferation-specific transcription factor. After FoxM1 protein activated, itcan regulate many key factors with the G1 / S phase,

6、G2 / M phase transition and mitotic cellcycle regulation. The research found that FoxM1 was continuously and highly expressed inmany cancers including glioma. Over-expression FoxM1 will disorder downstream targetgenes, s

7、uch as Survivin, Skp2, which can protect apoptosis, enhance cell proliferation, andinduce the tumor cells out of control in cell growth. Studies have proved that FoxM1 makeshigh expression of angiogenic factors VEGF and

8、promote glioma growth. In short, FoxM1might be a potential target sites of the glioma's gene therapy.
　　 In this paper, we used RNA interference to block the FoxM1 signaling pathway, andstudied the effect and mechani

9、sm of the inhibition of glioma proliferation. Therefore, weconstructed Ad hFoxM1 siRNA, and got a large number of high-titer adenovirus by using thetechnolog of CsCl density gradient eentrifugation. Make H4 and A172 cell

10、 infected by theadenovirus and the result showed that the adenovirus could successfully eliminate theexpression of FoxM1 in the mRNA level and at the protein level by using fluorescencequantitative PCR and western-blot d

11、emonstrating. Then we made the cell growth curve, foundthat the two cell proliferation had been inhibited. Further, we detected the mRNA level of cellcycle related genes Skp2 and CDC25B, apoptosis related genes Apaf-1 an

12、d inhibition ofapoptosis related genes Survivin. We found that in A172 cell line which FoxM1 was knockedout, the mRNA level of Skp2, CDC25B and Survivin was significantly reduced in contrast toApaf-1 significantly increa

13、sed, suggesting that cell proliferation had been inhibited and cellapoptosis increased. In summary, the results showed that FoxM1 was an important factor tothe formation and development of glioma. All the results still t