Effect Of Fufang Banmao Capsule Combined With Apatinib On Tumor Growth Of Osteosarcoma Xenograft Model Nude Mice Based On PI3K/AKT Pathway

Objective Through this study,researching the efficacy of Fufang Banmao capsule combined with apatinib and the regulation of PI3K/AKT signaling pathway in osteosarcoma xenograft model nude mice with mearuring tumor volume,tumor weight and body weight of osteosarcoma xenograft model nude mice.Methods The nude mice were divided into 6 groups according to the random number table method,with 10 mice in each group,namely model group(CMC group),apatinib group(APA group),apatinib combined with Fufang Banmao capsule low,middle and high dose groups(APAL,APAM and APAH group)and Fufang Banmao capsule middle dose group(M group).Each nude mouse was injected 1×10~6/200μL MNNG-HOS human osteosarcoma cells to the tibia bone.On the second day,intragastric administration was executed for 28 days.To calculate the tumor volume,the length and width of the tumor body were measured every four days.The weight of nude mice were weighted every week.After the last intragastric administration,the nude mice were killed,the tumor body were peeled off,the tumor weight were weighed,and the anti-tumor rates were calculated.One of the tumor was used for HE staining,and the other was used for q RT-PCR and Western Blot experiments.Results 1.Effect of drug administration on Tumor volume,anti-tumor rate,tumor weight and body weight:On 28th day,compared with the model group,the tumor volume in the drug group was significantly reduced(P<0.01).The anti-tumor rates of APA,APAL,APAM,APAH and M groups were 42%,48%,49%,55%and 39%.Compared with the model group,the tumor weight of the drug group was lower(P<0.05).The weight of nude mice in the model group was less than that in the drug group on the 28th day of intragastric administration(P<0.05).2.Effect of drug administration on Histomorphological:Under 100 times light microscope,osteosarcoma tissues in model group were closely arranged,and necrosis areas were rarely seen.In the drug group,there were many necrotic areas,and the necrotic areas showed a large piece of unstructured red-stained substance with some blue-stained nuclear fragments in the middle.3.Effect of drug administration on the expression on target m RNA:Compared with CMC group:the m RNA expression of VEGF in APA,APAH and M groups decreased(P<0.05),the expression of Bcl-2 m RNA in APA,APAL,APAM and APAH groups decreased(P<0.05).Compared with M group:the m RNA expression of Bcl-2 in APAM group decreased(P<0.05).4.Effect of drug administration on the expression on target protein:Compared with CMC group:the expression of p-PI3K and p-AKT protein in APA,APAL,APAM and APAH groups decreased(P<0.05),and the expression of VEGF and Bcl-2 protein in the medication group decreased(P<0.05).Compared with M group:the expression of p-PI3K protein in APA and APAM groups decreased(P<0.05),and that of p-AKT protein in APAM group decreased(P<0.05).Compared with APA group:the expression of p-AKT protein in APAL,APAM and APAH groups decreased(P<0.05),and the expression of Bcl-2 protein in APAH group decreased(P<0.05).Conclusion 1.Fufang Banmao capsule combined with apatinib can significantly inhibit the tumor growth of osteosarcoma xenograft model nude mice,reduce the weight loss caused by tumor growth,promote local necrosis in osteosarcoma tissue,reduce the expression of VEGF,Bcl-2m RNA and protein,and reduce the expression of p-PI3K and p-AKT protein;among them,Fufang Banmao capsule combined with apatinib decreased the protein expression of Bcl-2 in a dose-dependent manner2.Fufang Banmao capsule combined with apatinib can inhibits the tumor growth of osteosarcoma xenografts model in nude mice by inhibiting the PI3K/AKT signaling pathway and VEGF,Bcl-2 signaling factor.