Elevated glucose-6-phosphate dehydrogenase expression in the cervical cancer cases is associated with the cancerigenic event of high-risk human papillomaviruses
Elevated glucose-6-phosphate dehydrogenase expression in the cervical cancer cases is associated with the cancerigenic event of high-risk human papillomaviruses
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DOI：
10.1177/1535370214565971
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发表时间：
2015-10-01
影响因子：
3.2
通讯作者：
Xiyang, Yan-Bin
中科院分区：
文献类型：
--
作者：
Hu, Tao;Li, Ya-Shan;Xiyang, Yan-Bin
人乳头瘤病毒（HPV）是宫颈癌（CC）的重要致病因子，但其致病机制尚不清楚。葡萄糖-6-磷酸脱氢酶（G6 PD）在多种肿瘤细胞中升高。然而，到目前为止，没有可用的参考文献阐明G6 PD水平与HPV感染的CC之间的相关性。在本研究中，我们探讨了G6 PD在HPV感染引起的CC病理中的可能作用。本研究共纳入48例HPV + CC患者和63例健康女性。总的来说，高危型HPV（HR-HPV）感染的流行率是HPV-16，其次是HPV-18。采用免疫组化（IHC）、qRT-PCR和Western blot方法检测G6 PD在CC中的表达。回归分析显示，在30-40岁HR-HPV-16/18感染者中，G6 PD水平升高与CC的发生呈正相关。采用HPV 16 + Siha、HPV 18 + Hela和HPV-C33 A细胞系，并用体外开发的G6 PD缺陷型载体转染。MTT法和流式细胞仪检测G6 PD表达抑制后CC细胞的存活和凋亡情况。我们的数据显示，G6 PD下调诱导HPV 18 + Hela细胞的增殖较差，与HPV 16 + Siha和HPV-C33 A细胞相比，更多的凋亡。这些发现表明，HR-HPV +人CC组织和细胞系中的G6 PD表达在肿瘤生长和增殖中发挥重要作用。
The most important etiologic agent in the pathogenesis of cervical cancers (CCs) is human papillomavirus (HPV), while the mechanisms underlying are still not well known. Glucose-6-phosphate dehydrogenase (G6PD) is reported to elevate in various tumor cells. However, no available references elucidated the correlation between the levels of G6PD and HPV-infected CC until now. In the present study, we explored the possible role of G6PD in the pathology of CC induced by HPV infection. Totally 48 patients with HPV + CC and another 63 healthy women enrolled in the clinical were employed in the present study. Overall, prevalence of cervical infection with high-risk-HPV (HR-HPV) type examined was HPV-16, followed by HPV-18. The expressions of G6PD in CC samples were also detected by immunohistochemistry (IHC), qRT-PCR, and Western blot. Regression analysis showed elevated G6PD level was positively correlated with the CC development in 30-40 aged patients with HR-HPV-16/18 infection. The HPV16 + Siha, HPV18 + Hela, and HPV-C33A cell lines were employed and transfected with G6PD deficient vectors developed in vitro. MTT and flow cytometry were also employed to determine the survival and apoptosis of CC cells after G6PD expressional inhibition. Our data revealed that G6PD down-regulation induced poor proliferation and more apoptosis of HPV18 + Hela cells, when compared with that of HPV16 + Siha and HPV-C33A cells. These findings suggest that G6PD expressions in the HR-HPV + human CC tissues and cell lines play an important role in tumor growth and proliferation.