| Background:Hepatocellular carcinoma(HCC)is one of the common malignant tumors in China,with a high degree of malignancy,short survival time,easy recurrence and poor prognosis.Hepatocellular carcinoma is currently the 3rd leading cause of cancer death in the world.While the mortality of hepatic carcinoma ranks second,just next to lung cancer,in China.At present,chemotherapy as an important method for the treatment of liver cancer is easy to cause adverse reactions such as leukopenia,abnormal liver function,nausea and vomiting,loss of appetite,diarrhea,constipation and abdominal pain.And Chinese medicine can reduce the side effects of chemotherapy in patients,with increased treatment effects and reduce toxicity.It has been found that,Shen-Ling-Bai-Zhu Powder can relieve unwell symptoms and improve quality of life,in patients with hepatocellular carcinoma receiving chemotherapy.However,the related mechanism is still incompletely clear,and further study on the mechanism is necessary.Aim:To investigate the effects of SLBZP alone and in combination with Cytoxan(CTX)on tumor growth,malignant cell apoptosis and Akt/Nuclear Factor kappa B(NF-KB)signaling in a murine chemotherapeutic model of hepatocellular carcinoma(HCC).Methods:Sixty-four Kunming mice were subcutaneously injected with suspension of H22 hepatocellular carcinoma cells(2×107/mL)into the right anterior armpit.All mice were received intraperitoneal injection with cytoxan(CTX,200mg/kg)to establish the chemotherapeutic animal model of HCC.Mice were then randomized into eight study groups.One was treated with CTX(20mg/kg)alone(positive control),one with physiologic saline(untreated,negative control),three with SLBZP(6.00,3.00,1.50 g/kg),and three with SLBZP(6.00,3.00,1.50g/kg)plus CTX(0.02g/kg).Mice were allowed free access to food and water.The SLBZP(H),SLBZP(M)and SLBZP(L)treated groups received their treatments by intragastric administration of SLBZP aqueous solution once a day.The three combined treatment groups were treated with SLBZP as described above,plus intraperitoneal injections of CTX every 2 days.The CTX alone treated group was treated with CTX every 2 days.Finally,the untreated negative control group was injected with 0.2 mL/10g Sodium Chloride Physiological Solution as per the CTX alone group.All groups were treated for 14 days.Tumor size,histology and serum or tissue levels and/or mRNA expression of PDGF-BB,VEGF,Ang-1,Ang-2,Caspase-3,Caspase-7,Caspase-9,NF-KB,B-cell lymphoma-2(Bcl-2),B-cell lymphoma-extra large(Bcl-XL),Akt and phosphorylated Akt expression were documented at the end of treatment.Results:Tumor inhibitory ratios in CTX alone,SLBZP(H),SLBZP(H)plus CTX,and SLBZP(M)plus CTX were 52.39%,45.84%,58.41%and 52.77%,respectively.Tumor cell density was decreased in all treated groups but most apparent in the SLBZP(H)plus CTX group.Electron microscopic evidence of apoptosis was also most apparent in this group.Compared to untreated negative controls,the protein expression of PDGF-BB,VEGF,Ang-1,Ang-2,NF-KB,and XIAP were obviously lower in all treated groups.And the the protein expression of Caspase-3,Caspase-7 and Caspase-9 in all treated groups were obviously higher than those in negative controls.But their downstream signaling proteins and anti-apoptotic markers were lowest and pro-apoptotic markers highest in SLBZP(H)plus CTX treated mice.Conclusion:In this chemotheraptice animal model of HCC,SLBZP was most efficacious as adjunctive therapy and appears to act by inhibiting tumor growth promoters and anti-apoptotic proteins while enhancing pro-apoptotic proteins. |
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