In Vitro and In Vivo Synergistic Therapeutic Effect of Cisplatin with Human Papillomavirus16 E6/E7 CRISPR/Cas9 on Cervical Cancer Cell Line.
OBJECTIVE
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.


CONCLUSIONS
Collectively, our results suggested that HPV16 E6 + E7-CRISPR/Cas9 could be an effective sensitizer of CDDP chemotherapy in cervical cancer.
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.
Shuai
S
Zhen
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.
Jiao-Jiao
JJ
Lu
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.
Li-Jie
LJ
Wang
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.
Xiao-Min
XM
Sun
Department of Medical Imaging, The NO.2 People's Hospital of Lanzhou City, Lanzhou, China.
Jia-Qi
JQ
Zhang
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.
Xu
X
Li
School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: luowj@mail.xjtu.edu.cn.
Wen-Juan
WJ
Luo
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. Electronic address: zhaole2@mail.xjtu.edu.cn.
Le
L
Zhao