C-myc和HIF-1α蛋白在预测巨块型宫颈鳞癌新辅助化疗疗效中的作用

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摘要目的：研究C-myc和低氧诱导因子1α（HIF-1α）蛋白在巨块型宫颈鳞癌新辅助动脉化疗前后的变化以及与化疗疗效的相关性。方法：选取2007年1月-2012年8月在我院因巨块型（Ib2或IIa2期）宫颈鳞癌行新辅助动脉化疗和宫颈癌根治术的患者，共36例，新辅助动脉化疗方案均为顺铂、5-氟尿嘧啶加丝裂霉素的联合化疗。采用Western blot法检测宫颈鳞癌组织中C-myc和HIF-1α蛋白的特异性表达。采用免疫组织化学SP法检测宫颈鳞癌组织中C-myc和HIF-1α蛋白的细胞定位以及两种蛋白在化疗前后、化疗有效组和无效组中的表达差异。结果：①巨块型宫颈鳞癌新辅助动脉化疗的总有效率为52.7%。②C-myc和HIF-1α蛋白在化疗后宫颈鳞癌组织中的表达均显著低于化疗前（均P＜0.05）。③化疗前C-myc和HIF-1α蛋白的表达明显相关。④化疗前宫颈鳞癌组织中C-myc和HIF-1α蛋白的表达在化疗有效组中均比化疗无效组中高（均P＜0.05）。结论：巨块型宫颈鳞癌组织中C-myc和HIF-1α蛋白的表达可在新辅助动脉化疗前辅助预测化疗疗效。

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	吴均
	陈苗苗
	周青峰
	王颖
	朱雪琼

关键词 ： C-myc；低氧诱导因子1&alpha, ；宫颈肿瘤；新辅助化疗；疗效

Abstract：Objective: To study the change of C-myc and HIF-1α protein expression after neoadjuvant intra-arterial chemotherapy and explore the role of C-myc and HIF-1α protein in prediction on the response of neoadjuvant intra-arterial chemotherapy in bulky squamous cervical cancer. Methods: Thirty-six patients with stage Ib2 or IIa2 squamous cervical cancer who underwent neoadjuvant intra-arterial chemotherapy, combined cisplatin with 5-fluorouracil and mitomycin, and radical hysterectomy between 2007 and 2012 in Wenzhou Medical University were selected. Western blot was used to detect the specific expression of C-myc and HIF-1α protein. Then, streptavidin peroxidase (SP) immunohistochemical staining was used to detect the cellular localization of C-myc and HIF-1α protein and the difference of the expression of C-myc and HIF-1α protein between before and after neoadjuvant chemotherapy and between chemotherapy-response group and non-response group. Results: ①The total effective rate of neoadjuvant intra-arterial chemotherapy in bulky squamous cervical cancer was 52.7%. ②The expression of C-myc and HIF-1α protein in tumor cells after chemotherapy was significantly lower than that before chemotherapy (P<0.05). ③There was positive correlation between the expression of C-myc protein and HIF-1α protein before chemotherapy. ④The expression of C-myc and HIF-1α protein in chemotherapy-response group before chemotherapy was significantly higher than that in non-response group (P<0.05). Conclusion:
The expression of C-myc and HIF-1α protein in bulky squamous cervical cancer may be used as a predictor for response to neoadjuvant intra-arterial chemotherapy.

Key words： C-myc HIF-1α cervical neoplasms neoadjuvant chemotherapy response

收稿日期: 2014-08-19

基金资助:国家自然科学基金资助项目（30700195）。

通讯作者: 朱雪琼，教授，主任医师，博士生导师，Email：zjwzzxq@163.com。

作者简介: 吴均（1988-），男，浙江建德人，硕士生。现工作单位：温岭市第一人民医院。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2014/V44/I12/859

[1]Kim HS, Sardi JE, Katsumata N, et al. Efficacy of neoadjuvant chemotherapy in patients with FIGO stage IB1 to IIA cervical cancer: an international collaborative meta-analysis[J]. Eur J Surg Oncol, 2013, 39(2): 115-124.
[2]Ye Q, Yuan HX, Chen HL. Responsiveness of neoadjuvant chemotherapy before surgery predicts favorable prognosis for cervical cancer patients: a meta-analysis[J]. J Cancer Res Clin Oncol, 2013, 139(11): 1887-1898.
[3]Honjo S, Ajani JA, Scott AW, et al. Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer[J]. Int J Oncol, 2014, 45(2):567-574.
[4]Li S, Li Y, Hu R, et al. The mTOR inhibitor AZD8055 inhibits proliferation and glycolysis in cervical cancer cells[J]. Oncol Lett, 2013, 5(2): 717-721.
[5]Zou Z, Zhang J, Zhang H, et al. 3-Methyladenine can depress drug efflux transporters via blocking the PI3K-AKT-mTOR pathway thus sensitizing MDR cancer to chemotherapy[J]. J Drug Target, 2014, 22(9): 839-848.
[6]Li T, Tang L, Bian D, et al. Detection of hTERC and c-MYC genes in cervical epithelial exfoliated cells for cervical cancer screening [J]. Int J Mol Med, 2014, 33(5): 1289-1297.
[7]Liao LM, Sun XY, Liu AW, et al. Low expression of long noncoding XLOC 010588 indicates a poor prognosis and promotes proliferation through upregulation of c-Myc in cervical cancer[J]. Gynecol Oncol, 2014, 133(3): 616-623.
[8]Kasuya K, Tsuchida A, Nagakawa Y, et al. Hypoxia-induc-ible factor-1α expression and gemcitabine chemotherapy for pancreatic cancer[J]. Oncol Rep, 2011, 26(6): 1399-1406.
[9]Sun Q, Chen X, Ma J, et al. Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth[J]. Proc Natl Acad Sci USA, 2011, 108(10): 4129-4134.
[10]Zou S, Shen Q, Hua Y, et al. Proteomic identification of neo-adjuvant chemotherapy-related proteins in bulky stage IB-IIA squamous cervical cancer[J]. Reprod Sci, 2013, 20(11):1356-1364.
[11]吴均, 陈苗苗, 王颖, 等. mTOR-PKM2信号通路与宫颈鳞癌新辅助动脉化疗疗效的相关性研究[J]. 浙江医学, 2014, 36(2): 94-97.
[12]Hatano K, Yamaguchi S, Nimura K, et al. Residual prostate cancer cells after docetaxel therapy increase the tumorigenic potential via constitutive signaling of CXCR4, ERK1/2 and c-Myc[J]. Mol Cancer Res, 2013, 11(9): 1088-1100.
[13]Todorović-Raković N, Nešković-Konstantinović Z, Nikolić-Vukosavljević D. C-myc as a predictive marker for chemotherapy in metastatic breast cancer[J]. Clin Exp Med, 2012, 12(4): 217-223.
[14]唐金芝, 许君艳, 高琨, 等. C-MYC基因在宫颈上皮内瘤变及宫颈癌治疗前后的表达及其与HPV的相关性[J]. 广西医科大学学报, 2014, 31(1): 86-88.
[15]Yim EK, Lee KH, Kim CJ, et al. Analysis of differential protein expression by cisplatin treatment in cervical carcinoma cells[J]. Int J Gynecol Cancer, 2006, 16(2): 690-697.
[16]Nakamura J, Kitajima Y, Kai K, et al. Hypoxia-inducible factor-1alpha expression predicts the response to 5-fluoro-uracil-based adjuvant chemotherapy in advanced gastric cancer[J]. Oncol Rep, 2009, 22(4): 693-699.
[17]Ishikawa H, Sakurai H, Hasegawa M, et al. Expression of hypoxic-inducible factor 1alpha predicts metastasis-free survival after radiation therapy alone in stage IIIB cervical squamous cell carcinoma[J]. Int J Radiat Oncol Biol Phys,2004, 60(2): 513-521.
[18]Nakai H, Watanabe Y, Ueda H, et al. Hypoxia inducible factor 1-alpha expression as a factor predictive of efficacy of taxane/platinum chemotherapy in advanced primary epithelial ovarian cancer[J]. Cancer Lett, 2007, 251(1): 164-167.