沉默Stat3对卵巢癌细胞系OV2008恶性表型的影响

Effects of Blocking Stat3 on the Malignant Phenotype of Ovarian Cancer Cell Line OV2008

目的:探讨沉默信号转导和转录活化因子(Stat3)对卵巢癌细胞系OV2008恶性表型的影响。方法:腺病毒M4感染卵巢癌细胞系OV2008后,利用RT-PCR法检测Sta t3 mRNA的表达水平;Western blot法检测Stat3蛋白的表达水平;MTT法检测沉默Stat3对OV2008细胞的增殖抑制的影响;Transwell小室法检测沉默Stat3对OV2008细胞的侵袭运动能力的影响;流式细胞术检测沉默Stat3对OV2008细胞的凋亡的影响结果:RT-PCR以及Westetn blot结果显示,腺病毒M4感染卵巢癌细胞系OV2008后,OV2008细胞中的Sta3t mRNA以及Stat3蛋白的表达水平均明显降低;MTT结果显示,沉默Stat3表达后的OV2008细胞与空白对照组以及Ad5/dE1A病毒对照组的细胞相比,增殖能力明显减弱(P<0.05);Transwell小室法结果显示,沉默Stat3后的OV2008细胞12.64±7.10与空白对照组127.70±8.28以及Ad5/dElA病毒对照组137.80±9.78相比,侵袭运动能力明显减弱(P<0.05);流式细胞术检测结果显示,沉默Stat3表达后的OV2008细胞65.51±5.78与空白对照组10.73±4.28以及Ad5/dElA病毒对照组12.17±3.87相比,细胞凋亡率明显增加(P<0.05)。结论:沉默Stat3能明显抑制卵巢癌细胞系OV2008的增殖,降低其侵袭运动能力,并诱导其凋亡,即沉默Stat3能降低卵巢癌细胞系OV2008的恶性表型,提示Stat3可作为卵巢癌基因治疗的一个新的分子靶点。

Objective： To investigate the effects of blocking the signal transducer and activator of transcription 3 （ Stat3 ） on the malignant phenotype of ovarian cancer cell line OV2008. Methods： An ovarian cancer cell line OV2008 sample was infected with adenovirus M4. Reverse transcriptase polymerase chain reaction and Western blot assays were used to detect the Stat3 mRNA and protein levels, respectively. The effects of blocking Stat3 on cell proliferation, apoptotic rate, and cell invasion capacity were determined by MTT analysis, flow cytometry, and transwell migration assay, respectively. Results： The Stat3 mRNA and protein levels both notice- ably decreased in M4-infected OV2008 cells. The proliferation rates of the Stat3-blocked OV2008 cells were significantly slower than those of the control and Ad5/dE1A-infected groups （ P〈 0.05 ）. The invasion capacity of the Stat3-blocked OV2008 cells was （ 12.64 ± 9.1 ）. This value was much lower than those of the control （ 127.7 ±8.28 ） and Ad5/dE1A-infected groups （ 137.8 ± 9.78 ） （ P 〈 0.05 ）. The apoptosis rate of Stat3-blocked OV2008 cells was （ 65.51 ± 5.78 ）. This value was significantly higher than those of the control （ 10.73 ± 4.28 ） and Ad5/dE1A-infected groups （ 12.17 ± 3.87 ） （ P 〈 0.05 ）. Conclusion： Stat3 blockage led to decreased proliferation, increased apoptosis, and decreased invasion capacity in OV2008 cells. Hence, Stat3 may be a new target for ovarian cancer gene therapy.