Huang Yong-Wen, Zhou Yun, Lan Chun-Yan, Wang Yin, Feng Yan-Ling, Luo Rong-Zhen, Liu Ji-Hong
Department of Gynecology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
Drug Des Devel Ther. 2015 Nov 5;9:5949-56. doi: 10.2147/DDDT.S89810. eCollection 2015.
To establish the retroperitoneal lymph node (RLN) metastasis model of cervical carcinoma in rabbits and evaluate the relationship of vascular endothelial growth factor-C (VEGF-C) expression and the lymph node status.
Forty-eight rabbits were injected with VX2 cells or RPMI solution at muscular mucosae of the myometrium 0.5 cm away from the cervix. Animals were treated with or without cis-diamminedichloroplatinum(II) (cisplatin: DDP) and sacrificed on days 15, 21, and 27 post-VX2 or RPMI injections. Tumor mass and RLNs were examined histopathologically. Quantitative real-time PCR was used to examine the changes in VEGF-C mRNA expression. Levels of VEGF-C protein expression in tissues were determined using immunohistochemistry staining.
Development of VX2 cervical carcinoma and the RLNs metastasis was confirmed with pathological examination. Significantly increased tumor volume was observed on days 15, 21, and 27 postinjection (P<0.05). The enlargement of RLNs was found on day 21. Expression of VEGF-C was significantly upregulated in peripheral white blood cells, tumor mass, and RLNs in an association with cancer progression. DDP resulted in a suppression of VEGF-C expression, whereas the influences on tumor mass and lymphatic metastasis were insignificant.
Elevated VEGF-C expressions in peripheral white blood cells and RLNs are associated with tumor progression and lymphatic metastasis. DDP treatment inhibits VEGF-C expression and fails to protect against metastatic cervical cancer.
建立兔宫颈癌腹膜后淋巴结转移模型,评估血管内皮生长因子C(VEGF-C)表达与淋巴结状态的关系。
48只兔在距宫颈0.5 cm的子宫肌层肌黏膜处注射VX2细胞或RPMI溶液。对动物进行或不进行顺二氯二氨铂(顺铂:DDP)治疗,并在注射VX2或RPMI后第15、21和27天处死。对肿瘤块和腹膜后淋巴结进行组织病理学检查。采用定量实时PCR检测VEGF-C mRNA表达的变化。用免疫组织化学染色法测定组织中VEGF-C蛋白表达水平。
病理检查证实VX2宫颈癌及腹膜后淋巴结转移形成。注射后第15、21和27天观察到肿瘤体积显著增大(P<0.05)。第21天发现腹膜后淋巴结肿大。VEGF-C在外周白细胞、肿瘤块和腹膜后淋巴结中的表达随癌症进展而显著上调。DDP导致VEGF-C表达受到抑制,但其对肿瘤块和淋巴转移的影响不显著。
外周白细胞和腹膜后淋巴结中VEGF-C表达升高与肿瘤进展和淋巴转移有关。DDP治疗可抑制VEGF-C表达,但不能预防转移性宫颈癌。