Camptothecin Inhibits Progression Of Nasopharyngeal Carcinoma Cells Through Regulation Of TGF-β-induced PI-3Kinase/AKT Pathways

Background Nasopharyngeal carcinoma(NPC)is one kind of malignant tumors.Clinical observation and experimental studies have indicated that pathogenic factors of nasopharyngeal carcinoma are extensive,such as hereditary factors,virus infections,and environmental factors.Study has suggested that future perspectives for clinical research should include both prospective and observational cohort studies,which can assess the role of different risk factors in the development of NPC and the effectiveness of investigational treatments.Although previous reports have studied various anti-cancer drugs(docetaxel,Cisplatin,fluorouracil,gemcitabine,et al)for NPC treatment,the therapeutic outcomes are not particularly encouraging thus far for multidrug-resistant tumors of late period.Therefore,exploring new efficient anti-cancer agents and potential mechanism(s)of NPC migration and metastasis are still required to research the treatment of NPC.Camptothecin(C20H16N2O4)is one of anti-cancer drugs that has presented the efficacy for gastrointestinal and head and neck cancer therapy.In recent years,clinical pathologists have widely investigated the role of Camptothecin in the treatment of human cancer cells.A study showed that Camptothecin can induce human colon cancer cell death via down-regulation of mitogen-activated protein kinase phosphatase-1 and sustaining extracellular signal-regulated kinase 1/2 activation.In addition,Sun et al have showed that Camptothecin can inhibit prostate cancer cells growth and invasion via PI3K/AKT,alphaVbeta3/alphaVbeta5 and matrix metalloproteinases(MMP)-2/-9 signal pathway.Furthermore,pharmacodynamic and pharmacogenomic study revealed that Camptothecin conjugating the nanoparticle CRLX101 is efficient for the treatament of cancer.Although previous studies have indicated that efficacy of Camptothecin in solid tumors,seldom reports investigated the role of Camptothecin in NPCs.Moreover,no study reported the potential mechanism mediated by Camptothecin in the progression of NPC cells.Objective In this work,we investigated the efficacy of Camptothecin for NPS both in vitro and in vivo,as well as analyzed potential signal pathway mediated by Camptothecin in NPCs.This provides a new theoretical basis and direction for NPC therapy.Methods We treat NPC cell lines with different concentrations of CPT and observe CPT’s influence on the NPC cell proliferation and cell cycle;We treat NPC cell lines with different concentrations of CPT and observe CPT impact on the ability of invasion and metastasis of NPC cell line;Using qPCR,WB and immunohistochemical methods to explore the the effect of CPT on the PI3K/AKT signal pathway in the NPC cell line and tumor tissue;Using nude mice transplantation tumor model in vivo test the effect of CPT on NPC tumor growth and survival of mice.Results 1)Camptothecin treatment suppresses growth and arrests cell cycle of NPCs.2)Camptothecin treatment inhibits migration and invasion of NPCs.3)Camptothecin regulates NPCs growth by TGF-β-induced PI-3Kinase/AKT pathways.4)Camptothecin treatment inhibits tumor growth and prolongs animals’survival.Conclusions Camptothecin treatment can markedly suppress growth and arrest cell cycle of NPCs.Camptothecin treatment can inhibit migration and invasion via regulation of migration-related Vimentine,Fibronectin and E-cadherin expression levels in NPCs.Camptothecin regulates NPCs growth by TGF-β-induced PI-3Kinase/AKT pathway.Camptothecin treatment can inhibit tumor growth and prolong survival of NPS-bearing mice.In conclusion,this study explored the molecular mechanism of CPT inhibiting NPC,strengthened the antitumor efficacy of CPT,provided a theoretical basis for clinical CPT treatment and also offered a new development direction for the treatment of NPC.