Study On The Pharmacological Effects On Cervical Carcinoma And Associated Mechanism Of Cuprous Oxide Nanoparticles

Cervical carcinoma,is one of the most common malignancies in females,each year nearly 500,000 women were diagnosed with cervical cancer around the world.It is a great threaten to females.Cervical cancer is closely related to human papillomavirus high-risk types.The statistical data shows that HPV16,18,31,33,35,39,45,51,52,56,58,59,68,73 and 82 are associated with cervical cancer.The Infection rates in cervical cancer of HPV16/18 are 50% and 20%,respectively;the study have shown that the E6/E7 protein of high risk types of HPV in cervical cancer plays a vital role.E6 protein can induce degradation of P53,the tumor suppressors,through the ubiquitylation pathway.The E7 protein can phosphorylation the Rb protein to promotes tumor growth.The treatments for cervical cancer are mainly operation and chemotherapy.Surgery is mainly applicable to early patients in cervical cancer,especially for the stage I.Radiotherapy applied to most patients,but due to the side effects that radiation therapy can cause irreversible damage to the vagina and ovaries which limit the application of radiotherapy in young patients.Given cervical cancer is moderate sensitivity to chemotherapy,therefore,chemotherapy is used as adjuvant and palliative treatment for patients with advanced cervical cancer.Due to the current treatment options,the 5-year survival rate of patients with early stage cervical cancer can be as high as 95%,however,in,the 5-year survival rate of patients with advanced carcinoma is about 14%.Therefore,looking for new ways and new methods to treat cervical cancer has a significant meaning.It's well known,Nano,as a unit of a long-range,is only one in one billion meters,however,there are obvious changes in performance when the material becomes to the nanoscale,showing unexpected functions.Nanomedicine,as a branch of nanotechnology,refers to the application of theories and methods of nano-technology,on the basis of modern medicine and biology,is a new frontiers of medical research and clinical treatment.Nano-medicine has been researched in the following areas.such as nano-bio materials,nano-drug delivery system,Nano-medical diagnostics Nano-therapy and so on.Especially in the Nano-therapy,nano drug performance the advantages which traditional chemotherapy drugs do not have,such as smaller diameter,higher catalytic efficiency,stronger suction and so on.Anti-tumor nano drugs can be used as anti-tumor drugs which target tumor tissue,also can be applied to delivery system,which perform good application for tumor therapy in vivo and in vitro.Many studies confirm that nanoparticles can interfere the expression of those protein which take part in cell proliferation,apoptosis and transcription factor,to influence signal pathway to play a play a specific biological activity.Au NPS can inhibit tumor growth by inhibit MAPK signal pathway;Zn O can inhibit the Phosphorylation of AKT and Erk1/2,active JNK and P38,to suppress the migration and invasion of tumors.Many studies have shown that nano-drugs can target multiple signal pathways,have selective and pharmacological activity,therefore,there is a huge potential for exploration and research of nano-anticancer drugs.Cuprous oxide nanoparticles is a copper-containing nano-medicine,molecular formula is Cu2 O,its diameter is about 40nm~110nm,current studies have shown that,CONPs can inhibit the proliferation and metastasis of malignant melanoma,and the study confirm that CONPs can play anti-tumor role through apoptosis mediated by mitochondria signal pathway.In this study,we find that CONPs can strongly inhibit the cervical cancer cells proliferation,migration and invasion,it can also induce the apoptosis and arrest cell cycle.CONPs can inhibit the tumor growth in vivo and compared to cisplatin,CONPs group don't have the side effects such as lose weight which the cisplatin group have.In vitro and in vivo cellular level results suggest CONPs has good prospects in the treatment of cervical cancer.To better understand the mechanism of the anti-tumor of CONPs,we perform the transmission electron microscope to find that CONPs can cross the cell membrane,gathered in the cell's mitochondria,endoplasmic reticulum and other parts.We also find that With the increase of the concentration of CONPs,the production of autophagy also increased.Through the confocal laser scanning and the flow cytometry we found CONPs can decrease the mitochondria membrane potential by damage mitochondria,and confirm that with the increase of concentration of CONPs,the more amount of autophagosomes have been product.We use Western Blot to detect the expression of LC3,the marker of autophagy,the results are consistent with the former.Due to the close relation of autophagy and AKT/m TOR pathway,we further detected the related proteins such as AKT,p-AKT,m TOR,p-m TOR,and 4EBP1 to find that CONPs can inhibit the AKT/m TOR signal pathway,downregulated the phosphate level of AKT and m TOR to play its anti-tumor effects.In short,CONPs can inhibit the proliferation of cervical cancer,induce cell apoptosis,and can play a role by activating the AKT/m TOR pathway.