title: Oxymatrine inhibits the proliferation of CaSki cells via downregulating HPV16E7 expression.
abstract: Treatment of recurrent and metastatic cervical cancer remains a challenge, especially in developing countries, which lack efficient screening programs. HPV16E7 has been reported to play an important role in the development of cervical cancer. In recent years, oxymatrine, which was traditionally used as anti-malarial agent, has been shown to inhibit tumor growth with low toxicity to normal cells. In the present study, we investigated the mechanisms underlying the antitumor effect of oxymatrine in cervical cancer. The CCK-8 assay was used to compare the proliferation of untreated and oxymatrine-treated cervical cancer CaSki cells. Flow cytometry was applied to observe the effect of oxymatrine on apoptosis and the cell cycle distribution of CaSki cells. We used qRT-PCR and western blot analysis to determine the mRNA level and protein level of HPV16E7. The HPV16E7 siRNA inhibition was also performed to confirm the effect of downregulating HPV16E7 on the proliferation in CaSki cells. Our results revealed that oxymatrine-treated cells showed time-dependent and dose-dependent inhibition of proliferation and a significant increase in apoptosis. Oxymatrine arrested CaSki cells in G0/G1 phase and S phase while decreased the cells in G2/M phase. The expression of HPV16E7 was significantly downregulated in oxymatrine-treated cells compared with control cells. Knock-down of HPV16E7 effectively inhibited the proliferation of CaSki cells. In conclusion, our data suggest that oxymatrine inhibits cervical cancer growth via downregulation of HPV16E7. Oxymatrine can be considered to be a potential preventive and therapeutic target for cervical cancer.
authors.affiliation: Department of PET Center and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Pei
authors.affiliation: Department of Infection Control, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of PET Center and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of PET Center and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Fuyan
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of PET Center and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of PET Center and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of PET Center and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of PET Center and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of PET Center and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Yijia
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei 430022, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics; D050725:Papillomavirus E7 Proteins / Q000235:genetics*; D011807:Quinolizines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000962:Antimalarials; D000970:Antineoplastic Agents; D050725:Papillomavirus E7 Proteins; D011807:Quinolizines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C059731:oncogene protein E7, Human papillomavirus type 16; C037573:oxymatrine; D000093842:Matrines