VEGF—C对宫颈癌凋亡影响的研究进展(3)
流式细胞术检测细胞周期后显示，随着预处理VEGF-C浓度的升高，DDP诱导的宫颈癌细胞HeLa凋亡率明显下降，G1期细胞减少，S期细胞增多，提示VEGF-C抑制DDP诱导HeLa的凋亡可能与细胞周期调节密切相关。p53对细胞周期和细胞凋亡起着重要作用，是细胞周期检查点相关基因。p53参与了细胞从增殖到死亡的过程，能调控细胞生长，对于预防和治疗胆管癌、肝癌、胃癌等疾病具有重要作用[25]。VEGF-C对DDP的作用可能是使p53表达下调，从而无法实现p53诱导受损细胞进入G1/G0期，使细胞周期的保护和修复机制无法启动，导致DNA受损的细胞无限增殖，这可能是VEGF-C促使HeLa由G0或G1期进入S期，逃避细胞凋亡的一个原因。细胞周期相关基因数量众多，是否还存在其他基因与VEGF-C抗凋亡和多药耐药有关尚需进一步探索。
4 结语
VEGF-C在宫颈癌发生、发展、转移、复发和预后等方面起着重要作用，它通过NF-κB和PI3K信号通路来发挥抗凋亡作用，然而，是否存在其他信号通路与其抗凋亡有关有待进一步探索。VEGF-C也参与肿瘤的多药耐药，但具体机制尚不清楚，从参与NF-κB信号通路、PI3K信号通路及细胞周期的各种相关基因及蛋白入手，可能会为宫颈癌耐药机制的研究提供重要思路，这些基因和蛋白将成为宫颈癌治疗的靶点，为宫颈癌的治疗及预防开辟一条重要通路。
[参考文献]
[1] Chien MH，Ku CC，Johansson G，et al.Vascular endothelial growth factor-C(VEGF-C)promotes angiogenesis by induction of COX-2 in leukemic cells via the VEGF-R3/JNK/AP-1 pathway[J].Carcinogenesis，2009，30(12)：2005-2013.
[2] Smith NR，Baker D，James NH，et al.Vascular endothelial growth factor receptors VEGFR-2 and VEGFR-3 are localized primarily to the vasculature in human primary solid cancers[J].Clin Cancer Res，2010，16( 14)：3548-3561.
[3] Guo X，Chen Y，Xu Z，et al.Prognostic significance of VEGF-C expression in correlation with COX-2，lymphatic microvessel density，and clinicopathologic characteristics in human non-small cell lung cancer[J].Acta Biochim Biophys Sin(Shanghai)，2009，41(3)：217-222.
[4] Chen H，Suo K，Cheng Y，et al.Vascular endothelial growth factor C enhances cervical cancer migration and invasion via activation of focal adhesion kinase[J].Gynecol Endocrinol，2013，29(1)：20-24.
[5] Liu D，Li L，Zhang XX，et al.Six1 Promotes Tumor Lymphangiogenesis by Coordinating TGFβ Signals That Increase Expression of VEGF-C[J].Cancer Res，2014，74(19)：5597-5607.
[6] Demei Ma，Xiangxin Li，Yongping Xu，et al.Vascular endothelial growth factor C expression is closely correlated with lymph node recurrence and poor prognosis in patients with early stage cervical cancer[J].J Int Med Res，2013，41(5)：1541-1549.
[7] Ma DM，Xu YP，Zhu L.Expression of vascular endothelial growth factor C correlates with a poor prognosis based on analysis of prognostic factors in patients with cervical carcinomas[J].J Obstet Gynaecol Res，2011，37(11)：1519-1524.
[8] Biedka M，Makarewicz R，Marszatek A，et al.Labeling of microvessel density，lymphatic vessel density and potential role of proangiogenic and lymphangiogenic factors as a predictive/prognostic factors after radiotherapy in patients with cervical cancer[J].Eur J Gynaecol Oncol，2011，33(4)：399-405. (袁芳 任黔川)
4 结语
VEGF-C在宫颈癌发生、发展、转移、复发和预后等方面起着重要作用，它通过NF-κB和PI3K信号通路来发挥抗凋亡作用，然而，是否存在其他信号通路与其抗凋亡有关有待进一步探索。VEGF-C也参与肿瘤的多药耐药，但具体机制尚不清楚，从参与NF-κB信号通路、PI3K信号通路及细胞周期的各种相关基因及蛋白入手，可能会为宫颈癌耐药机制的研究提供重要思路，这些基因和蛋白将成为宫颈癌治疗的靶点，为宫颈癌的治疗及预防开辟一条重要通路。
[参考文献]
[1] Chien MH，Ku CC，Johansson G，et al.Vascular endothelial growth factor-C(VEGF-C)promotes angiogenesis by induction of COX-2 in leukemic cells via the VEGF-R3/JNK/AP-1 pathway[J].Carcinogenesis，2009，30(12)：2005-2013.
[2] Smith NR，Baker D，James NH，et al.Vascular endothelial growth factor receptors VEGFR-2 and VEGFR-3 are localized primarily to the vasculature in human primary solid cancers[J].Clin Cancer Res，2010，16( 14)：3548-3561.
[3] Guo X，Chen Y，Xu Z，et al.Prognostic significance of VEGF-C expression in correlation with COX-2，lymphatic microvessel density，and clinicopathologic characteristics in human non-small cell lung cancer[J].Acta Biochim Biophys Sin(Shanghai)，2009，41(3)：217-222.
[4] Chen H，Suo K，Cheng Y，et al.Vascular endothelial growth factor C enhances cervical cancer migration and invasion via activation of focal adhesion kinase[J].Gynecol Endocrinol，2013，29(1)：20-24.
[5] Liu D，Li L，Zhang XX，et al.Six1 Promotes Tumor Lymphangiogenesis by Coordinating TGFβ Signals That Increase Expression of VEGF-C[J].Cancer Res，2014，74(19)：5597-5607.
[6] Demei Ma，Xiangxin Li，Yongping Xu，et al.Vascular endothelial growth factor C expression is closely correlated with lymph node recurrence and poor prognosis in patients with early stage cervical cancer[J].J Int Med Res，2013，41(5)：1541-1549.
[7] Ma DM，Xu YP，Zhu L.Expression of vascular endothelial growth factor C correlates with a poor prognosis based on analysis of prognostic factors in patients with cervical carcinomas[J].J Obstet Gynaecol Res，2011，37(11)：1519-1524.
[8] Biedka M，Makarewicz R，Marszatek A，et al.Labeling of microvessel density，lymphatic vessel density and potential role of proangiogenic and lymphangiogenic factors as a predictive/prognostic factors after radiotherapy in patients with cervical cancer[J].Eur J Gynaecol Oncol，2011，33(4)：399-405. (袁芳 任黔川)