Zinc Finger Nuclease Combines with Cisplatin and Trichostatin A Enhances the Antitumor Potency in Cervical Cancer Cells

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Author(s): Ci Ren, Chun Gao, Xiaomin Li, Hui Shen, Liming Wang, Da Zhu, Peng Wu, Ding Ma, Hui Wang*, Wencheng Ding*.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

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Background: Cervical cancer is the third-most common malignant tumor among women worldwide, which seriously endangers the life and health of Chinese women. The primary etiological factor of cervical cancer is persistent infection with high-risk human papillomavirus (HR-HPV), particularly HPV16 and HPV18. HR-HPV express oncoproteins E6 and E7, both of which play key roles in the progression of cervical carcinogenesis. Zinc Finger Nucleases (ZFNs) targeting HPVE7 induce specific shear of the E7 gene, weakening the malignant biological effects, hence showing great potential for clinical transformation. In order to better application in the clinical setting, it is necessary to explore an integrative strategy.

Methods: We hypothesize that some chemotherapy drugs somehow make DNA more sensible to editing by enhancing ZFN’s gene editing effectiveness. Here, we tested the combined effects of ZFNs with two chemotherapy drugs in vitro and in vitro.

Result: Results showed that the combined treatment induced the rate of apoptosis by about two times more than that of ZFNs used alone in SiHa and HeLa cells. The co-treatment suppressed colony formation ability by more than 80%, and both chemotherapy drugs coordinated with ZFNs to down regulate HPV16/18E7 and elevate RB1 expression. Additionally, subcutaneous tumor inhibition experiment demonstrated strong synergistic effects in the chemotherapy drugs and ZFNs.

Conclusion: Our results demonstrate that some chemotherapy drugs can augment the biological effects of ZFNs and the combined treatment may be an effective therapy for cervical malignancy lesions.

Keywords: Zinc finger nucleases, chemotherapy drugs, E7, RB1, human papillomavirus, synergistic, siha, HeLa.

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(E-pub Ahead of Print)
DOI: 10.2174/1871520618666180509152222
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