目的:血管生成是肿瘤生长和转移的关键介质,CDC25B在包括三阴性乳腺癌(Triple-Negative Breast Cancer,TNBC)等恶性肿瘤作为肿瘤癌基因,但其对血管生成的生物学作用知之甚少,本研究旨在探讨CDC25B在TNBC血管生成中的确切功能和作用机制...目的:血管生成是肿瘤生长和转移的关键介质,CDC25B在包括三阴性乳腺癌(Triple-Negative Breast Cancer,TNBC)等恶性肿瘤作为肿瘤癌基因,但其对血管生成的生物学作用知之甚少,本研究旨在探讨CDC25B在TNBC血管生成中的确切功能和作用机制。方法:生信数据库分析CDC25B及其上游调控分子miR-141-3p在TNBC肿瘤组织中的表达,采用qRT-PCR分析CDC25B和miR-141-3p在TNBC细胞系中的表达。利用CCK-8和血管形成实验分析HUVEC细胞的增殖和血管形成能力,并通过Western blot检测VEGFA、VEGFR-2和VEGFR-3蛋白的表达。双荧光素酶报告实验被用于探索CDC25B和miR-141-3p之间的特异性相互作用。结果:本研究发现CDC25B在TNBC中表达上调,其高表达可以激活VEGF信号通路,沉默CDC25B后显著抑制了HUVEC细胞的增殖和血管生成,并降低了VEGFA、VEGFR-2和VEGFR-3蛋白的表达。此外,miR-141-3p在TNBC中表达下调,可以靶向抑制CDC25B的表达。过表达CDC25B可以逆转miR-141-3p过表达对HUVEC细胞增殖和血管生成的抑制作用。结论:miR-141-3p靶向CDC25B抑制VEGF通路抑制TNBC血管生成,为miR-141-3p/CDC25B/VEGF通路可能作为TNBC抗血管生成治疗的新选择提供理论依据。展开更多
Objective To observe the effect of artesunate (Art) on the proliferation of human esophageal carcinoma cell line Eca109 and the growth of transplantation tumors of nude mice, and explore the possible involvement of CD...Objective To observe the effect of artesunate (Art) on the proliferation of human esophageal carcinoma cell line Eca109 and the growth of transplantation tumors of nude mice, and explore the possible involvement of CDC25A expression in the cell cycle arrest induced by Art. Methods MTT method was employed to detect the proliferation of the Eca109 cells and normal human peripheral blood mononuclear cells (hPBMC) after Art treatment. Cell cycle of the tumor cells was assayed by flow cytometry. Inhibitory effects of Art on the transplanted tumor on nude mice were observed by mass weight, volume and morphological method. The expression of CDC25A in the Eca109 cells was examined by RT-PCR and Western blotting. Results Art significantly inhibited the proliferation of Eca109 with the IC50 of (68.80±0.76) μmol/L, while it had weaker effect on that of the hPBMC induced by Con A. At lower doses of Art, the number of Eca109 cells during G0/G1 was increased, and that at S phase was reduced dramatically. However, when the concentration was up to 100 μmol/L, most of cells were arrested at G2/M phase. The volume and weight of transplanted tumor receiving Art treatment were smaller and lower than those of control group, with the maximal inhibitory rate of 76.4%. Art dramatically inhibited the mRNA as well as protein expressions of CDC25A in the Eca109 cells. Conclusion Art can inhibit the proliferation of tumor cells and transplanted tumor without apparent side effect, possibly by the mechanism of modulating cell cycle through CDC25A down-regulation.展开更多
文摘目的:血管生成是肿瘤生长和转移的关键介质,CDC25B在包括三阴性乳腺癌(Triple-Negative Breast Cancer,TNBC)等恶性肿瘤作为肿瘤癌基因,但其对血管生成的生物学作用知之甚少,本研究旨在探讨CDC25B在TNBC血管生成中的确切功能和作用机制。方法:生信数据库分析CDC25B及其上游调控分子miR-141-3p在TNBC肿瘤组织中的表达,采用qRT-PCR分析CDC25B和miR-141-3p在TNBC细胞系中的表达。利用CCK-8和血管形成实验分析HUVEC细胞的增殖和血管形成能力,并通过Western blot检测VEGFA、VEGFR-2和VEGFR-3蛋白的表达。双荧光素酶报告实验被用于探索CDC25B和miR-141-3p之间的特异性相互作用。结果:本研究发现CDC25B在TNBC中表达上调,其高表达可以激活VEGF信号通路,沉默CDC25B后显著抑制了HUVEC细胞的增殖和血管生成,并降低了VEGFA、VEGFR-2和VEGFR-3蛋白的表达。此外,miR-141-3p在TNBC中表达下调,可以靶向抑制CDC25B的表达。过表达CDC25B可以逆转miR-141-3p过表达对HUVEC细胞增殖和血管生成的抑制作用。结论:miR-141-3p靶向CDC25B抑制VEGF通路抑制TNBC血管生成,为miR-141-3p/CDC25B/VEGF通路可能作为TNBC抗血管生成治疗的新选择提供理论依据。
文摘Objective To observe the effect of artesunate (Art) on the proliferation of human esophageal carcinoma cell line Eca109 and the growth of transplantation tumors of nude mice, and explore the possible involvement of CDC25A expression in the cell cycle arrest induced by Art. Methods MTT method was employed to detect the proliferation of the Eca109 cells and normal human peripheral blood mononuclear cells (hPBMC) after Art treatment. Cell cycle of the tumor cells was assayed by flow cytometry. Inhibitory effects of Art on the transplanted tumor on nude mice were observed by mass weight, volume and morphological method. The expression of CDC25A in the Eca109 cells was examined by RT-PCR and Western blotting. Results Art significantly inhibited the proliferation of Eca109 with the IC50 of (68.80±0.76) μmol/L, while it had weaker effect on that of the hPBMC induced by Con A. At lower doses of Art, the number of Eca109 cells during G0/G1 was increased, and that at S phase was reduced dramatically. However, when the concentration was up to 100 μmol/L, most of cells were arrested at G2/M phase. The volume and weight of transplanted tumor receiving Art treatment were smaller and lower than those of control group, with the maximal inhibitory rate of 76.4%. Art dramatically inhibited the mRNA as well as protein expressions of CDC25A in the Eca109 cells. Conclusion Art can inhibit the proliferation of tumor cells and transplanted tumor without apparent side effect, possibly by the mechanism of modulating cell cycle through CDC25A down-regulation.
