Adenovirus-mediated transfer of HPV 16 E6/E7 antisense RNA combined with cisplatin inhibits cellular growth and induces apoptosis in HPV-positive head and neck cancer cells
Adenovirus-mediated transfer of HPV 16 E6/E7 antisense RNA combined with cisplatin inhibits cellular growth and induces apoptosis in HPV-positive head and neck cancer cells
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DOI：
10.1038/s41417-018-0024-3
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发表时间：
2018-10-01
影响因子：
6.4
通讯作者：
Nibu, Ken-ich
中科院分区：
文献类型：
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作者：
Kojima, Yasutaka;Otsuki, Naoki;Nibu, Ken-ich
人乳头状瘤病毒（HPV）感染是头颈部肿瘤的重要致病因素。我们探讨了反义HPV RNA转录物用于基因治疗的潜在用途及其与顺铂（CDDP）联合治疗HPV阳性HNC的效果。我们利用腺病毒载体Ad-E6/E7-AS，将HPV 16型E6和E7基因的反义RNA导入携带HPV 16的UM-SCC-47细胞和HPV阴性的YCU-T892细胞中。然后，我们分析了Ad-E7-AS的引入对细胞和肿瘤生长的影响以及与CDDP的体内外协同效应。Ad-E6/E7-AS感染UM-SCC-47细胞后，细胞生长受到抑制，但对YCU-T892细胞生长无明显影响。感染Ad-E7-AS后，E7蛋白表达受到抑制，p53和pRb蛋白表达增加。与Ad-E7-AS或CDDP单独处理相比，CDDP与Ad-E7-AS组合显著抑制细胞生长和致瘤性。Ad-E7-AS联合CDDP治疗显著减少了已建立的皮下肿瘤的体积。HPV 16 E7反义RNA转染联合顺铂治疗HPV 16阳性HNC可能是一种有效的治疗方法。
Human papillomavirus (HPV) infection has been identified as an etiologic factor of head and neck cancers (HNCs). We explored the potential use of antisense HPV RNA transcripts for gene therapy and its effect in combination with cisplatin (CDDP) for HPV-positive HNCs. We introduced the antisense RNA transcripts of the E6 and E7 genes of HPV type 16 into UM-SCC-47 cells harboring HPV 16 and YCU-T892 cells that were HPV-negative using a recombinant adenoviral vector, Ad-E6/E7-AS. We then analyzed the effects of the introduction of Ad-E7-AS on cell and tumor growth and the synergistic effect with CDDP in vitro and in vivo. After infection of Ad-E6/E7-AS, the cellular growth of UM-SCC-47 cells were suppressed, but not that of YCU-T892 cells. E7 protein expression was suppressed, and p53 and pRb protein expression increased after infection of Ad-E7-AS. Cell growth and tumorigenicity were greatly suppressed in combination with CDDP compared with Ad-E7-AS or CDDP treatment alone in vitro. Ad-E7-AS combined with CDDP treatment significantly reduced the volumes of established subcutaneous tumors. Transfection with HPV 16 E7 antisense RNA combined with CDDP treatment might be a potentially useful approach to the therapy of HPV 16-positive HNC.