Preliminary Screening Of Killing Effect Of 800 Kinds Of Small Molecular Drugs On Cervical Cancer Cells

ObjectiveThe incidence and mortality of cervical cancer are increasing year by year.Although with the continuous development of scientific research,gynecological tumor has made a lot of progress in medical treatment,but for patients who have received surgery,radiotherapy and chemotherapy for advanced cervical cancer disease progression,there is still a lack of new treatment options.It is particularly urgent to establish a comprehensive prevention and control system combining cervical cancer screening and human papillomavirus vaccination so as to reduce the burden of cervical cancer on Chinese women.The development and research of preventive and therapeutic vaccines are extremely urgent,and the development of molecular targeted drugs is urgent.Inspired by the "new use of old drugs",800 chemical entities approved by the Food and Drug Administration(FDA)were selected in this study to preliminarily screen the killing effect of these 800 small-molecule drugs on cervical cancer.The purpose of this study was to screen out the old drugs with killing effect on cervical cancer and to provide early reference data for the application of such drugs in the treatment of cervical cancer.MethodThe drug retargeting model of 800 small molecule drugs was constructed.Six cell lines of cervical cancer were cultured,Hela,Siha,MS751,C33A,Caski,me-180.The six cell lines were respectively planked(about 10,000 cells per well).After the planking cells adhered to the wall,the small molecule drug was diluted to 2?M/L,and 20u was added to 96-well plate cells of 80u per well after dosing of incubated with the cells in 37? temperature box after 48 hours,the CCK8 method to read the value of cells,and calculate the cell sufirst rvival rate six types of cervical cancer cells were cultured,paged and dosed from the 800 small molecule drugs in the fda-approved "drug repositioning" drug pool.FindingsAmong the 800 small-molecule drugs,18 drugs with strong killing effect on cervical cancer cells were selected,which were as follows:Mitoxantrone,Tubercidin,Epirubicin hydrochloride,Fludarabine Phosphate,Homoharringtonine,D-Pantothenic acid sodium salt,Proflavine Hemisulfate and MitoxantroneHydrochloride,Gemcitabine,Vagistat,Flurbiprofen,Vinorelbine Tartrate,(+)-Emetine dihydrochloride hydrate,Hesperidin,Doxorubicin hydrochloride,Podophyllotoxin,Gramicidin,Auranofin.(the order does not include the degree to which it kills cervical cancer cells).Some of the drugs are approved chemotherapy drugs,and some drugs have been reported to have anti-other malignant tumors,but there has been no report on the treatment of cervical cancer.After literature search of these 18 small molecule drugs,two drugs were selected as the key drugs to screen.The two drugs are respectively kinofen and hesperidin after gradient dilution,kinofen and hesperidin had stronger killing effect on cervical cancer cells than second-line chemotherapy drugs at 2?M/L concentration.ConclusionIn this study,we found that Auranofin and Hesperidin have strong killing effect on cervical cancer cells.However,whether these two drugs were effective in vivo and their mechanism still need further exploration and experimental study.