顺铂与人乳头瘤病毒16 E6/E7 CRISPR/Cas9对宫颈癌细胞系的体内外协同治疗作用
In Vitro and In Vivo Synergistic Therapeutic Effect of Cisplatin with Human Papillomavirus16 E6/E7 CRISPR/Cas9 on Cervical Cancer Cell Line.
作者信息
Zhen Shuai, Lu Jiao-Jiao, Wang Li-Jie, Sun Xiao-Min, Zhang Jia-Qi, Li Xu, Luo Wen-Juan, Zhao Le
机构信息
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Medical Imaging, The NO.2 People's Hospital of Lanzhou City, Lanzhou, China.
出版信息
Transl Oncol. 2016 Dec;9(6):498-504. doi: 10.1016/j.tranon.2016.10.002. Epub 2016 Oct 28.
PURPOSE
Human papillomavirus (HPV) type 16 is one of the major etiologic factors of cervical cancer. Our study aims to investigate the potentiality of the antiviral clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated Cas9 system (CRISPR/Cas9) targeting the E6 and E7 oncogenes of HPV16 as a potential chemosensitizer of cisplatin (cis-diaminedichloroplatinum II; CDDP) for cervical cancer.
METHODS
Specifically, the therapeutic efficacy of combination of CDDP and HPV16 E6 + E7-CRISPR/Cas9 was assessed in cervical cancer cells and cervical cancer xenograft models.
RESULTS
In vitro experiments showed that long-term exposure of SiHa cells to the HPV16 E6 + E7-CRISPR/Cas9 induced apoptosis, and its pro-apoptosis effect became more obvious when combined with CDDP. In vivo study found the efficacy of the combination of HPV16 E6 + E7-CRISPR/Cas9 and CDDP were superior to either of the treatments in term of apoptosis induction and metastasis inhibition.
CONCLUSION
Collectively, our results suggested that HPV16 E6 + E7-CRISPR/Cas9 could be an effective sensitizer of CDDP chemotherapy in cervical cancer.
目的
人乳头瘤病毒16型（HPV16）是宫颈癌的主要病因之一。我们的研究旨在探究靶向HPV16的E6和E7致癌基因的抗病毒成簇规律间隔短回文重复序列（CRISPR）/CRISPR相关Cas9系统（CRISPR/Cas9）作为宫颈癌顺铂（顺二氯二氨铂II；CDDP）潜在化学增敏剂的可能性。
方法
具体而言，在宫颈癌细胞和宫颈癌异种移植模型中评估CDDP与HPV16 E6 + E7-CRISPR/Cas9联合治疗的疗效。
结果
体外实验表明，将SiHa细胞长期暴露于HPV16 E6 + E7-CRISPR/Cas9会诱导细胞凋亡，当与CDDP联合使用时，其促凋亡作用更加明显。体内研究发现，HPV16 E6 + E7-CRISPR/Cas9与CDDP联合使用在诱导凋亡和抑制转移方面的疗效优于任何一种单一治疗。
结论
总体而言，我们的结果表明HPV16 E6 + E7-CRISPR/Cas9可能是宫颈癌CDDP化疗的有效增敏剂。
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