| Introduction: nasopharyngeal carcinoma(NPC) is a common head and neckmalignancy in the south of China.. In the early stage, radiotherapy is considered aspreferred treatment protocol. Chemotherapy and surgery often considered as auxiliarytherapy of patients with advanced cancer. But radiotherapy also have some limitations,it not only kill cancer cells but also damage normal tissues, and residue many sequelasuch as radioactive otitis media, osteoradionecrosis of bones and loss of taste. Manypatients are not discovered until the NPC is at a late-stage, so if only depend onradiotherapy is not sufficient. common side effects of chemotherapy drugs cisplatinand5-FU include harm kidney, ear, nerve and heart. So it is hot to search less toxicand effective auxiliary therapy for NPC.Curcumin is a polyphenol derived from the rhizome of Curcuma longa, and oftenconsumed as a dietary supplement and colourant. Meanwhile, curcumin possessanti-inflammatory, anti-oxidant, anti-HIV virus, anti-infection and anti-cancer activity.It has great potential to explore to new drugs for anti-cancer. However, curcumin hasbeen limited by its poor solubility and bioavailability, thus, Pharmaceutical College ofFujian Medical University synthesized an analogue of curcumin----FM0807. So far,reports about NPC treat with curcumin are few. Our studies analyze anti-NPC activityof FM0807and its mechanism and provide assistance for clinical therapy.Objective: To evaluate whether FM0807would suppress the growth of NPC invitro and in vivo, and study its mechanism to probe a novel molecular target therapyfor NPC. Methods:(1)NPC cells were treated with curcumin and FM0807, and MTT,Trypan Blue notation and colony formation assays were used to evaluate the effect ofthe drugs.(2)colony formation assays and western blot were used to analyzeproliferative activity and P-ERK1/2expression of Rhek cells.(3) Hoechest33342/PIanalysis and western blot were applied to determine apoptosis and shape of NPC cellswith FM0807treatment.(4)RT-PCR and western blot were used to evaluate the mRNAand protein levels of ERK1/2and EGFR with FM0807treatment, western blot alsoused to analysis whether FM0807can inhibit ERK/MAPK signal mediated by EGF.(5)Co-immunoprecipitation assays were used to analysis whether FM0807can affect thechaperone function of Hsp90.(6)western blot were used to analysis whether FM0807downregulation of Raf-1/MEK/ERK signaling pathway.(7) We established CNE2NPC xenografts in nude mice and FM0807were given to measure tumor volume andweights. Western blot were used to show the effect of FM0807on Raf-1/MEK/ERKsignaling pathway in vivo.Results:(1) proliferation of NPC cells with FM0807incubation was inhibited in adose-dependent way. Colony formation assays showed the inhibition effct of FM0807on NPC cells is superior to curcumin.(2) FM0807did not affect colony formation ofRhek, In addition, P-ERK1/2protein expression was also not varied.(3) Cell cyclearrest and apoptosis were induced by FM0807.(4) FM0807treatment did not affectmRNA and protein expression of ERK and EGFR of CNE2cells, but P-ERK1/2wasinhibited by FM0807.(5) Raf-1and MEK1/2coprecitated with Hsp90were depletedwhich induced by FM0807.(6)FM0807downregulation of Raf-1/MEK/ERK signalingpathway in vitro.(7) FM0807inhibition of tumor growth in vivo via downregulaion ofRaf-1/MEK/ERK signaling pathway.Conclusion:(1)FM0807show little impact on normal cells, but it can inhibitsNPC cells proliferation, induces cell cycle arrest and apoptosis.(2) FM0807also cansuppresses NPC growth in vivo.(3)the anti-NPC mechanism may be FM0807inhibitsRaf-1/MEK/ERK signaling pathway through down-regulation of Hsp90client proteins. |
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